Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Adhesion Molecules: Master Controllers of the Circulatory System

Eric P. Schmidt, Wolfgang M. Kuebler, Warren L. Lee, Gregory P. Downey

10.1002/cphy.c150020

Source: null

Published online: March 2016

Full Article on Wiley Online Library



ABSTRACT

This manuscript will review our current understanding of cellular adhesion molecules (CAMs) relevant to the circulatory system, their physiological role in control of vascular homeostasis, innate and adaptive immune responses, and their importance in pathophysiological (disease) processes such as acute lung injury, atherosclerosis, and pulmonary hypertension. This is a complex and rapidly changing area of research that is incompletely understood. By design, we will begin with a brief overview of the structure and classification of the major groups of adhesion molecules and their physiological functions including cellular adhesion and signaling. The role of specific CAMs in the process of platelet aggregation and hemostasis and leukocyte adhesion and transendothelial migration will be reviewed as examples of the complex and cooperative interplay between CAMs during physiological and pathophysiological processes. The role of the endothelial glycocalyx and the glycobiology of this complex system related to inflammatory states such as sepsis will be reviewed. We will then focus on the role of adhesion molecules in the pathogenesis of specific disease processes involving the lungs and cardiovascular system. The potential of targeting adhesion molecules in the treatment of immune and inflammatory diseases will be highlighted in the relevant sections throughout the manuscript. © 2016 American Physiological Society. Compr Physiol 6:945‐973, 2016.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Combinatorial Possibilities of Integrins. [Adapted from (218) with permission.]
Figure 2. Figure 2. Leukocyte adhesion and transmigration. [Adapted from (317) with permission.] For clarity, adhesion molecules, LBRC, microtubules, and caveolae are only illustrated on some endothelial cells and leukocytes in this figure.
Figure 3. Figure 3. Structure of ESL.
Figure 4. Figure 4. Glycosylation patterns of adhesion molecules.


Figure 1. Combinatorial Possibilities of Integrins. [Adapted from (218) with permission.]


Figure 2. Leukocyte adhesion and transmigration. [Adapted from (317) with permission.] For clarity, adhesion molecules, LBRC, microtubules, and caveolae are only illustrated on some endothelial cells and leukocytes in this figure.


Figure 3. Structure of ESL.


Figure 4. Glycosylation patterns of adhesion molecules.
References
 1. Aalto K , Autio A , Kiss EA , Elima K , Nymalm Y , Veres TZ , Marttila‐Ichihara F , Elovaara H , Saanijoki T , Crocker PR , Maksimow M , Bligt E , Salminen TA , Salmi M , Roivainen A , Jalkanen S . Siglec‐9 is a novel leukocyte ligand for vascular adhesion protein‐1 and can be used in PET imaging of inflammation and cancer. Blood 118: 3725‐3733, 2011.
 2. Adamson RH . Permeability of frog mesenteric capillaries after partial pronase digestion of the endothelial glycocalyx. J Physiol 428: 1‐13, 1990.
 3. Agouridakis P , Kyriakou D , Alexandrakis MG , Prekates A , Perisinakis K , Karkavitsas N , Bouros D . The predictive role of serum and bronchoalveolar lavage cytokines and adhesion molecules for acute respiratory distress syndrome development and outcome. Respir Res 3: 25, 2002.
 4. Alcaide P , Auerbach S , Luscinskas FW . Neutrophil recruitment under shear flow: It's all about endothelial cell rings and gaps. Microcirculation 16: 43‐57, 2009.
 5. Alcaide P , Newton G , Auerbach S , Sehrawat S , Mayadas TN , Golan DE , Yacono P , Vincent P , Kowalczyk A , Luscinskas FW . p120‐Catenin regulates leukocyte transmigration through an effect on VE‐cadherin phosphorylation. Blood 112: 2770‐2779, 2008.
 6. Allingham MJ , van Buul JD , Burridge K . ICAM‐1‐mediated, Src‐ and Pyk2‐dependent vascular endothelial cadherin tyrosine phosphorylation is required for leukocyte transendothelial migration. J Immunol 179: 4053‐4064, 2007.
 7. An G , Wang H , Tang R , Yago T , McDaniel JM , McGee S , Huo Y , Xia L . P‐selectin glycoprotein ligand‐1 is highly expressed on Ly‐6Chi monocytes and a major determinant for Ly‐6Chi monocyte recruitment to sites of atherosclerosis in mice. Circulation 117: 3227‐3237, 2008.
 8. Anderson DC , Springer TA . Leukocyte adhesion deficiency: An inherited defect in the Mac‐1, LFA‐1, and p150,95 glycoproteins. Annu Rev Med 38: 175‐194, 1987.
 9. Andrews RK , Berndt MC . Bernard‐Soulier syndrome: An update. Semin Thromb Hemost 39: 656‐662, 2013.
 10. Arcangeli ML , Frontera V , Aurrand‐Lions M . Function of junctional adhesion molecules (JAMs) in leukocyte migration and homeostasis. Arch Immunol Ther Exp 61: 15‐23, 2013.
 11. Arita‐Okubo S , Kim‐Kaneyama JR , Lei XF , Fu WG , Ohnishi K , Takeya M , Miyauchi A , Honda H , Itabe H , Miyazaki T , Miyazaki A . Role of Hic‐5 in the formation of microvilli‐like structures and the monocyte‐endothelial interaction that accelerates atherosclerosis. Cardiovasc Res 105: 361‐371, 2015.
 12. Arumugam TV , Granger DN , Mattson MP . Stroke and T‐cells. NeuromolecularMed 7: 229‐242, 2005.
 13. Arumugam TV , Salter JW , Chidlow JH , Ballantyne CM , Kevil CG , Granger DN . Contributions of LFA‐1 and Mac‐1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion. AmJPhysiol Heart CircPhysiol 287: H2555‐H2560, 2004.
 14. Askari JA , Buckley PA , Mould AP , Humphries MJ . Linking integrin conformation to function. J Cell Sci 122: 165‐170, 2009.
 15. Aurrand‐Lions M , Lamagna C , Dangerfield JP , Wang S , Herrera P , Nourshargh S , Imhof BA . Junctional adhesion molecule‐C regulates the early influx of leukocytes into tissues during inflammation. J Immunol 174: 6406‐6415, 2005.
 16. Axelsson J , Xu D , Kang BN , Nussbacher JK , Handel TM , Ley K , Sriramarao P , Esko JD . Inactivation of heparan sulfate 2‐O‐sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice. Blood 120: 1742‐1751, 2012.
 17. Bao X , Moseman EA , Saito H , Petryniak B , Thiriot A , Hatakeyama S , Ito Y , Kawashima H , Yamaguchi Y , Lowe JB , von Andrian UH , Fukuda M . Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes. Immunity 33: 817‐829, 2010.
 18. Barczyk M , Carracedo S , Gullberg D . Integrins. Cell Tissue Res 339: 269‐280, 2010.
 19. Barreiro O , Yanez‐Mo M , Serrador JM , Montoya MC , Vicente‐Manzanares M , Tejedor R , Furthmayr H , Sanchez‐Madrid F . Dynamic interaction of VCAM‐1 and ICAM‐1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157: 1233‐1245, 2002.
 20. Barringhaus KG , Phillips JW , Thatte JS , Sanders JM , Czarnik AC , Bennett DK , Ley KF , Sarembock IJ . α4β1 integrin (VLA‐4) blockade attenuates both early and late leukocyte recruitment and neointimal growth following carotid injury in apolipoprotein E−/− mice. JVascRes 41: 252‐260, 2004.
 21. Bartelds B , van Loon RL , Mohaupt S , Wijnberg H , Dickinson MG , Boersma B , Takens J , van AM , Berger RM . Mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension. Chest 141: 651‐660, 2012.
 22. Baum B , Georgiou M . Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling. J Cell Biol 192: 907‐917, 2011.
 23. Becker KJ . Anti‐leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke. CurrMedResOpin 18(Suppl 2): s18‐s22, 2002.
 24. Bednar MM , Gross CE , Balazy M , Falck JR . Antineutrophil strategies. Neurology 49: S20‐S22, 1997.
 25. Bennett HS , Luft JH , Hampton JC . Morphological classifications of vertebrate blood capillaries. Am J Physiol 196: 381‐390, 1959.
 26. Bistrup A , Bhakta S , Lee JK , Belov YY , Gunn MD , Zuo FR , Huang CC , Kannagi R , Rosen SD , Hemmerich S . Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L‐selectin. J Cell Biol 145: 899‐910, 1999.
 27. Bitsch A , Klene W , Murtada L , Prange H , Rieckmann P . A longitudinal prospective study of soluble adhesion molecules in acute stroke. Stroke 29: 2129‐2135, 1998.
 28. Blann A , Kumar P , Krupinski J , McCollum C , Beevers DG , Lip GY . Soluble intercellular adhesion molecule‐1, E‐selectin, vascular cell adhesion molecule‐1 and von Willebrand factor in stroke. Blood CoagulFibrinolysis 10: 277‐284, 1999.
 29. Breitling S , Buelow R , Kuebler WM . B cells promote pulmonary hypertension and vascular remodeling in the monocrotaline rat model. Am J Respir Crit Care Med 187: A4619, 2013.
 30. Brieher WM , Yap AS . Cadherin junctions and their cytoskeleton(s). Curr Opin Cell Biol 25: 39‐46, 2013.
 31. Brockhausen I , Schachter H , Stanley P . O‐GalNAc Glycans. In: Varki A , Cummings RD , Esko JD , Freeze HH , Stanley P , Bertozzi CR , Hart GW , Etzler ME , editors. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press, 2009, pp. 115‐126.
 32. Bruehl RE , Springer TA , Bainton DF . Quantitation of L‐selectin distribution on human leukocyte microvilli by immunogold labeling and electron microscopy. J Histochem Cytochem 44: 835‐844, 1996.
 33. Bunting M , Harris ES , McIntyre TM , Prescott SM , Zimmerman GA . Leukocyte adhesion deficiency syndromes: Adhesion and tethering defects involving beta 2 integrins and selectin ligands. Curr Opin Hematol 9: 30‐35, 2002.
 34. Burger PC , Wagner DD . Platelet P‐selectin facilitates atherosclerotic lesion development. Blood 101: 2661‐2666, 2003.
 35. Burnham EL , Moss M , Harris F , Brown LA . Elevated plasma and lung endothelial selectin levels in patients with acute respiratory distress syndrome and a history of chronic alcohol abuse. Crit Care Med 32: 675‐679, 2004.
 36. Burns AR , Smith CW , Walker DC . Unique structural features that influence neutrophil emigration into the lung. Physiol Rev 83: 309‐336, 2003.
 37. Burton VJ , Butler LM , McGettrick HM , Stone PC , Jeffery HC , Savage CO , Rainger GE , Nash GB . Delay of migrating leukocytes by the basement membrane deposited by endothelial cells in long‐term culture. Exp Cell Res 317: 276‐292, 2011.
 38. Butler LM , Rainger GE , Nash GB . A role for the endothelial glycosaminoglycan hyaluronan in neutrophil recruitment by endothelial cells cultured for prolonged periods. Exp Cell Res 315: 3433‐3441, 2009.
 39. Cabodi S , Di Stefano P , Leal Mdel P , Tinnirello A , Bisaro B , Morello V , Damiano L , Aramu S , Repetto D , Tornillo G , Defilippi P . Integrins and signal transduction. Adv Exp Med Biol 674: 43‐54, 2010.
 40. Calfee CS , Eisner MD , Parsons PE , Thompson BT , Conner ER , Jr. , Matthay MA , Ware LB , Network NARDSCT. Soluble intercellular adhesion molecule‐1 and clinical outcomes in patients with acute lung injury. Intensive Care Med 35: 248‐257, 2009.
 41. Carman CV , Sage PT , Sciuto TE , de la Fuente MA , Geha RS , Ochs HD , Dvorak HF , Dvorak AM , Springer TA . Transcellular diapedesis is initiated by invasive podosomes. Immunity 26: 784‐797, 2007.
 42. Carman CV , Springer TA . A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167: 377‐388, 2004.
 43. Carraway MS , Welty‐Wolf KE , Kantrow SP , Huang YC , Simonson SG , Que LG , Kishimoto TK , Piantadosi CA . Antibody to E‐ and L‐selectin does not prevent lung injury or mortality in septic baboons. Am J Respir Crit Care Med 157: 938‐949, 1998.
 44. Cavallaro U , Dejana E . Adhesion molecule signalling: Not always a sticky business. Nat Rev Mol Cell Biol 12: 189‐197, 2011.
 45. Cera MR , Fabbri M , Molendini C , Corada M , Orsenigo F , Rehberg M , Reichel CA , Krombach F , Pardi R , Dejana E . JAM‐A promotes neutrophil chemotaxis by controlling integrin internalization and recycling. J Cell Sci 122: 268‐277, 2009.
 46. Chappell D , Dorfler N , Jacob M , Rehm M , Welsch U , Conzen P , Becker BF . Glycocalyx protection reduces leukocyte adhesion after ischemia/reperfusion. Shock 34: 133‐139, 2010.
 47. Chappell D , Jacob M , Paul O , Rehm M , Welsch U , Stoeckelhuber M , Conzen P , Becker BF . The glycocalyx of the human umbilical vein endothelial cell: An impressive structure ex vivo but not in culture. Circ Res 104: 1313‐1317, 2009.
 48. Chappell D , Jacob M , Rehm M , Stoeckelhuber M , Welsch U , Conzen P , Becker BF . Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx. Biol Chem 389: 79‐82, 2008.
 49. Chatterjee S , Sharma A , Mukherjee D . PAR‐1 antagonists: Current state of evidence. J Thromb Thrombolysis 35: 1‐9, 2013.
 50. Chopp M , Zhang RL , Chen H , Li Y , Jiang N , Rusche JR . Postischemic administration of an anti‐Mac‐1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke 25: 869‐875, 1994.
 51. Cinamon G , Shinder V , Shamri R , Alon R . Chemoattractant signals and beta 2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migration. J Immunol 173: 7282‐7291, 2004.
 52. Cioffi DL , Pandey S , Alvarez DF , Cioffi EA . Terminal sialic acids are an important determinant of pulmonary endothelial barrier integrity. Am J Physiol Lung Cell Mol Physiol 302: L1067‐L1077, 2012.
 53. Collins RG , Velji R , Guevara NV , Hicks MJ , Chan L , Beaudet AL . P‐Selectin or intercellular adhesion molecule (ICAM)‐1 deficiency substantially protects against atherosclerosis in apolipoprotein E‐deficient mice. JExpMed 191: 189‐194, 2000.
 54. Colvin KL , Cripe PJ , Ivy DD , Stenmark KR , Yeager ME . Bronchus‐associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies. AmJRespirCrit Care Med 188: 1126‐1136, 2013.
 55. Connolly ES, Jr. , Winfree CJ , Prestigiacomo CJ , Kim SC , Choudhri TF , Hoh BL , Naka Y , Solomon RA , Pinsky DJ . Exacerbation of cerebral injury in mice that express the P‐selectin gene: identification of P‐selectin blockade as a new target for the treatment of stroke. CircRes 81: 304‐310, 1997.
 56. Connolly ES, Jr. , Winfree CJ , Springer TA , Naka Y , Liao H , Yan SD , Stern DM , Solomon RA , Gutierrez‐Ramos JC , Pinsky DJ . Cerebral protection in homozygous null ICAM‐1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. JClinInvest 97: 209‐216, 1996.
 57. Cool CD , Kennedy D , Voelkel NF , Tuder RM . Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human immunodeficiency virus infection. HumPathol 28: 434‐442, 1997.
 58. Corada M , Chimenti S , Cera MR , Vinci M , Salio M , Fiordaliso F , De Angelis N , Villa A , Bossi M , Staszewsky LI , Vecchi A , Parazzoli D , Motoike T , Latini R , Dejana E . Junctional adhesion molecule‐A‐deficient polymorphonuclear cells show reduced diapedesis in peritonitis and heart ischemia‐reperfusion injury. Proc Natl Acad Sci U S A 102: 10634‐10639, 2005.
 59. Corada M , Mariotti M , Thurston G , Smith K , Kunkel R , Brockhaus M , Lampugnani MG , Martin‐Padura I , Stoppacciaro A , Ruco L , McDonald DM , Ward PA , Dejana E . Vascular endothelial‐cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci U S A 96: 9815‐9820, 1999.
 60. Corso G , Figueiredo J , Biffi R , Trentin C , Bonanni B , Feroce I , Serrano D , Cassano E , Annibale B , Melo S , Seruca R , De Lorenzi F , Ferrara F , Piagnerelli R , Roviello F , Galimberti V . E‐cadherin germline mutation carriers: Clinical management and genetic implications. Cancer Metastasis Rev 33: 1081‐1094, 2014.
 61. Coughlin SR . Protease‐activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Thrombolysis 3: 1800‐1814, 2005.
 62. Cullen PJ . Post‐translational regulation of signaling mucins. Curr Opin Struct Biol 21: 590‐596, 2011.
 63. Cybulsky MI , Iiyama K , Li H , Zhu S , Chen M , Iiyama M , Davis V , Gutierrez‐Ramos JC , Connelly PW , Milstone DS . A major role for VCAM‐1, but not ICAM‐1, in early atherosclerosis. JClinInvest 107: 1255‐1262, 2001.
 64. D'Alessio FR , Tsushima K , Aggarwal NR , West EE , Willett MH , Britos MF , Pipeling MR , Brower RG , Tuder RM , McDyer JF , King LS . CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest 119: 2898‐2913, 2009.
 65. Dahal BK , Kosanovic D , Kaulen C , Cornitescu T , Savai R , Hoffmann J , Reiss I , Ghofrani HA , Weissmann N , Kuebler WM , Seeger W , Grimminger F , Schermuly RT . Involvement of mast cells in monocrotaline‐induced pulmonary hypertension in rats. Respir Res 12: 60, 2011.
 66. Dai E , Liu LY , Wang H , McIvor D , Sun YM , Macaulay C , King E , Munuswamy‐Ramanujam G , Bartee MY , Williams J , Davids J , Charo I , McFadden G , Esko JD , Lucas AR . Inhibition of chemokine‐glycosaminoglycan interactions in donor tissue reduces mouse allograft vasculopathy and transplant rejection. PloS One 5: e10510, 2010.
 67. Dangerfield J , Larbi KY , Huang MT , Dewar A , Nourshargh S . PECAM‐1 (CD31) homophilic interaction up‐regulates alpha6beta1 on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane. J Exp Med 196: 1201‐1211, 2002.
 68. Day AJ , Prestwich GD . Hyaluronan‐binding proteins: Tying up the giant. J Biol Chem 277: 4585‐4588, 2002.
 69. De Luca M , Dunlop LC , Andrews RK , Flannery JV, Jr. , Ettling R , Cumming DA , Veldman GM , Berndt MC . A novel cobra venom metalloproteinase, mocarhagin, cleaves a 10‐amino acid peptide from the mature N terminus of P‐selectin glycoprotein ligand receptor, PSGL‐1, and abolishes P‐selectin binding. J Biol Chem 270: 26734‐26737, 1995.
 70. DeGraba TJ . The role of inflammation after acute stroke: Utility of pursuing anti‐adhesion molecule therapy. Neurology 51: S62‐S68, 1998.
 71. Dejana E , Tournier‐Lasserve E , Weinstein BM . The control of vascular integrity by endothelial cell junctions: Molecular basis and pathological implications. Dev Cell 16: 209‐221, 2009.
 72. del Zoppo GJ , Hallenbeck JM . Advances in the vascular pathophysiology of ischemic stroke. ThrombRes 98: 73‐81, 2000.
 73. Dengler V , Downey GP , Tuder RM , Eltzschig HK , Schmidt EP . Neutrophil intercellular communication in acute lung injury. Emerging roles of microparticles and gap junctions. Am J Respir Cell Mol Biol 49: 1‐5, 2013.
 74. Ding Z , Issekutz TB , Downey GP , Waddell TK . L‐selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: Implications for cellular activation during adhesion and migration. Blood 101: 4245‐4252, 2003.
 75. Dirnagl U , Niwa K , Sixt G , Villringer A . Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging. Stroke 25: 1028‐1038, 1994.
 76. Ditlevsen DK , Kolkova K . Signaling pathways involved in NCAM‐induced neurite outgrowth. Adv Exp Med Biol 663: 151‐168, 2010.
 77. Doerschuk CM . Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8: 71‐88, 2001.
 78. Doerschuk CM . The role of CD18‐mediated adhesion in neutrophil sequestration induced by infusion of activated plasma in rabbits. Am J Respir Cell Mol Biol 7: 140‐148, 1992.
 79. Doerschuk CM , Downey GP , Doherty DE , English D , Gie RP , Ohgami M , Worthen GS , Henson PM , Hogg JC . Leukocyte and platelet margination within microvasculature of rabbit lungs. J Appl Physiol 68: 1956‐1961, 1990.
 80. Doherty DE , Worthen GS . Lipopolysaccharide‐induced monocyte retention in the lungs of rabbits. Role of cell stiffness and the CD11/CD18 leukocyte adhesion complex. Chest 105: 108S, 1994.
 81. Dong ZM , Brown AA , Wagner DD . Prominent role of P‐selectin in the development of advanced atherosclerosis in ApoE‐deficient mice. Circulation 101: 2290‐2295, 2000.
 82. Downey GP , Doherty DE , Schwab B , Elson EL , Henson PM , Worthen GS . Retention of leukocytes in capillaries: role of cell size and deformability. J Appl Physiol 69: 1767‐1778, 1990.
 83. Downey GP , Worthen GS , Henson PM , Hyde DM . Neutrophil sequestration and migration in localized pulmonary inflammation. Capillary localization and migration across the interalveolar septum. Am Rev Respir Dis 147: 168‐176, 1993.
 84. Doyle NA , Bhagwan SD , Meek BB , Kutkoski GJ , Steeber DA , Tedder TF , Doerschuk CM . Neutrophil margination, sequestration, and emigration in the lungs of L‐selectin‐deficient mice. J Clin Invest 99: 526‐533, 1997.
 85. Dustin ML . The cellular context of T cell signaling. Immunity 30: 482‐492, 2009.
 86. Dutka AJ , Kochanek PM , Hallenbeck JM . Influence of granulocytopenia on canine cerebral ischemia induced by air embolism. Stroke 20: 390‐395, 1989.
 87. Ebong EE , Macaluso FP , Spray DC , Tarbell JM . Imaging the endothelial glycocalyx in vitro by rapid freezing/freeze substitution transmission electron microscopy. Arterioscler Thromb Vasc Biol 31: 1908‐1915, 2011.
 88. Ehrlich P . Beiträge zur Kenntnis der granulierten Bindegewebszellen und der eosinophilen Leukozyten. Arch Anat Physiol 3: 166‐169, 1879.
 89. Emerich DF , Dean RL, III , Bartus RT . The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct? ExpNeurol 173: 168‐181, 2002.
 90. Enlimomab Acute Stroke Trial Investigators. Use of anti‐ICAM‐1 therapy in ischemic stroke: Results of the Enlimomab Acute Stroke Trial. Neurology 57: 1428‐1434, 2001.
 91. Eriksson EE , Xie X , Werr J , Thoren P , Lindbom L . Importance of primary capture and L‐selectin‐dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo. JExpMed 194: 205‐218, 2001.
 92. Erzurum SC , Downey GP , Doherty DE , Schwab B, III , Elson EL , Worthen GS . Mechanisms of lipopolysaccharide‐induced neutrophil retention. Relative contributions of adhesive and cellular mechanical properties. J Immunol 149: 154‐162, 1992.
 93. Esko JD , Lindahl U . Molecular diversity of heparan sulfate. J Clin Invest 108: 169‐173, 2001.
 94. Evans R , Patzak I , Svensson L , De Filippo K , Jones K , McDowall A , Hogg N . Integrins in immunity. J Cell Sci 122: 215‐225, 2009.
 95. Farahani E , Patra HK , Jangamreddy JR , Rashedi I , Kawalec M , Rao Pariti RK , Batakis P , Wiechec E . Cell adhesion molecules and their relation to (cancer) cell stemness. Carcinogenesis 35: 747‐759, 2014.
 96. Farha S , Sharp J , Asosingh K , Park M , Comhair SA , Tang WH , Thomas J , Farver C , Hsieh F , Loyd JE , Erzurum SC . Mast cell number, phenotype, and function in human pulmonary arterial hypertension. PulmCirc 2: 220‐228, 2012.
 97. Fassbender K , Mossner R , Motsch L , Kischka U , Grau A , Hennerici M . Circulating selectin‐ and immunoglobulin‐type adhesion molecules in acute ischemic stroke. Stroke 26: 1361‐1364, 1995.
 98. Feng D , Nagy JA , Pyne K , Dvorak HF , Dvorak AM . Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 187: 903‐915, 1998.
 99. Ferreira AM , McNeil CJ , Stallaert KM , Rogers KA , Sandig M . Interleukin‐1beta reduces transcellular monocyte diapedesis and compromises endothelial adherens junction integrity. Microcirculation 12: 563‐579, 2005.
 100. Fiszer U , Korczak‐Kowalska G , Palasik W , Korlak J , Gorski A , Czlonkowska A . Increased expression of adhesion molecule CD18 (LFA‐1beta) on the leukocytes of peripheral blood in patients with acute ischemic stroke. Acta NeurolScand 97: 221‐224, 1998.
 101. Frijns CJ , Kappelle LJ . Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke 33: 2115‐2122, 2002.
 102. Frijns CJ , Kappelle LJ , van GJ , Nieuwenhuis HK , Sixma JJ , Fijnheer R . Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis. Stroke 28: 2214‐2218, 1997.
 103. Fu G , Wang W , Luo BH . Overview: Structural biology of integrins. Methods Mol Biol 757: 81‐99, 2012.
 104. Furuya K , Takeda H , Azhar S , McCarron RM , Chen Y , Ruetzler CA , Wolcott KM , DeGraba TJ , Rothlein R , Hugli TE , del Zoppo GJ , Hallenbeck JM . Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti‐human intercellular adhesion molecule‐1 antibody: a bedside‐to‐bench study. Stroke 32: 2665‐2674, 2001.
 105. Gahmberg CG . Leukocyte adhesion: CD11/CD18 integrins and intercellular adhesion molecules. Curr Opin Cell Biol 9: 643‐650, 1997.
 106. Galkina E , Ley K . Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol 27: 2292‐2301, 2007.
 107. Gardel ML , Schneider IC , Aratyn‐Schaus Y , Waterman CM . Mechanical integration of actin and adhesion dynamics in cell migration. Annu Rev Cell Dev Biol 26: 315‐333, 2010.
 108. Gawaz M , Langer H , May AE . Platelets in inflammation and atherogenesis. JClinInvest 115: 3378‐3384, 2005.
 109. Gebb SA , Graham JA , Hanger CC , Godbey PS , Capen RL , Doerschuk CM , Wagner WW, Jr . Sites of leukocyte sequestration in the pulmonary microcirculation. J Appl Physiol 79: 493‐497, 1995.
 110. Gerard A , van der Kammen RA , Janssen H , Ellenbroek SI , Collard JG . The Rac activator Tiam1 controls efficient T‐cell trafficking and route of transendothelial migration. Blood 113: 6138‐6147, 2009.
 111. Goggs R , Williams CM , Mellor H , Poole AW . Platelet Rho GTPases‐a focus on novel players, roles and relationships. Biochem J 466: 431‐442, 2015.
 112. Gomez‐Gaviro M , Dominguez‐Luis M , Canchado J , Calafat J , Janssen H , Lara‐Pezzi E , Fourie A , Tugores A , Valenzuela‐Fernandez A , Mollinedo F , Sanchez‐Madrid F , Diaz‐Gonzalez F . Expression and regulation of the metalloproteinase ADAM‐8 during human neutrophil pathophysiological activation and its catalytic activity on L‐selectin shedding. J Immunol 178: 8053‐8063, 2007.
 113. Goodman SL , Picard M . Integrins as therapeutic targets. Trends Pharmacol Sci 33: 405‐412, 2012.
 114. Grieve AP , Krams M . ASTIN: A Bayesian adaptive dose‐response trial in acute stroke. ClinTrials 2: 340‐351, 2005.
 115. Grommes J , Alard JE , Drechsler M , Wantha S , Morgelin M , Kuebler WM , Jacobs M , von HP , Markart P , Wygrecka M , Preissner KT , Hackeng TM , Koenen RR , Weber C , Soehnlein O . Disruption of platelet‐derived chemokine heteromers prevents neutrophil extravasation in acute lung injury. AmJRespirCrit Care Med 185: 628‐636, 2012.
 116. Gros A , Ollivier V , Ho‐Tin‐Noe B . Platelets in inflammation: regulation of leukocyte activities and vascular repair. Front Immunol 5: 678, 2014.
 117. Hammer DA . Adhesive dynamics. J Biomech Eng 136: 021006, 2014.
 118. Harris AK , Ergul A , Kozak A , Machado LS , Johnson MH , Fagan SC . Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke. BMCNeurosci 6: 49, 2005.
 119. Harris ES , Weyrich AS , Zimmerman GA . Lessons from rare maladies: Leukocyte adhesion deficiency syndromes. Curr Opin Hematol 20: 16‐25, 2013.
 120. Hassoun PM , Adnot S . Update in pulmonary vascular diseases 2011. Am J Respir Crit Care Med 185: 1177‐1182, 2012.
 121. Hassoun PM , Mouthon L , Barbera JA , Eddahibi S , Flores SC , Grimminger F , Jones PL , Maitland ML , Michelakis ED , Morrell NW , Newman JH , Rabinovitch M , Schermuly R , Stenmark KR , Voelkel NF , Yuan JX , Humbert M . Inflammation, growth factors, and pulmonary vascular remodeling. J Am CollCardiol 54: S10‐S19, 2009.
 122. Hayward NJ , Elliott PJ , Sawyer SD , Bronson RT , Bartus RT . Lack of evidence for neutrophil participation during infarct formation following focal cerebral ischemia in the rat. ExpNeurol 139: 188‐202, 1996.
 123. Heath D , Trueman T , Sukonthamarn P . Pulmonary mast cells in mitral stenosis. CardiovascRes 3: 467‐471, 1969.
 124. Heath D , Yacoub M . Lung mast cells in plexogenic pulmonary arteriopathy. J ClinPathol 44: 1003‐1006, 1991.
 125. Henry CB , Duling BR . Permeation of the luminal capillary glycocalyx is determined by hyaluronan. Am J Physiol 277: H508‐H514, 1999.
 126. Heuberger J , Birchmeier W . Interplay of cadherin‐mediated cell adhesion and canonical Wnt signaling. Cold Spring Harb Perspect Biol 2: a002915, 2010.
 127. Hironaka E , Hongo M , Sakai A , Mawatari E , Terasawa F , Okumura N , Yamazaki A , Ushiyama Y , Yazaki Y , Kinoshita O . Serotonin receptor antagonist inhibits monocrotaline‐induced pulmonary hypertension and prolongs survival in rats. CardiovascRes 60: 692‐699, 2003.
 128. Hoffmann J , Yin J , Kukucka M , Yin N , Saarikko I , Sterner‐Kock A , Fujii H , Leong‐Poi H , Kuppe H , Schermuly RT , Kuebler WM . Mast cells promote lung vascular remodeling in pulmonary hypertension. Eur Respir J 37: 1400‐1410, 2010.
 129. Huang AJ , Manning JE , Bandak TM , Ratau MC , Hanser KR , Silverstein SC . Endothelial cell cytosolic free calcium regulates neutrophil migration across monolayers of endothelial cells. J Cell Biol 120: 1371‐1380, 1993.
 130. Huang J , Choudhri TF , Winfree CJ , McTaggart RA , Kiss S , Mocco J , Kim LJ , Protopsaltis TS , Zhang Y , Pinsky DJ , Connolly ES, Jr . Postischemic cerebrovascular E‐selectin expression mediates tissue injury in murine stroke. Stroke 31: 3047‐3053, 2000.
 131. Hulpiau P , van Roy F . Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol 41: 349‐369, 2009.
 132. Huo Y , Xia L . P‐selectin glycoprotein ligand‐1 plays a crucial role in the selective recruitment of leukocytes into the atherosclerotic arterial wall. Trends CardiovascMed 19: 140‐145, 2009.
 133. Hurn PD , Subramanian S , Parker SM , Afentoulis ME , Kaler LJ , Vandenbark AA , Offner H . T‐ and B‐cell‐deficient mice with experimental stroke have reduced lesion size and inflammation. JCerebBlood Flow Metab 27: 1798‐1805, 2007.
 134. Huveneers S , Danen EH . Adhesion signaling ‐ crosstalk between integrins, Src and Rho. J Cell Sci 122: 1059‐1069, 2009.
 135. Hyun YM , Lefort CT , Kim M . Leukocyte integrins and their ligand interactions. Immunol Res 45: 195‐208, 2009.
 136. Iannone F , Riccardi MT , Guiducci S , Bizzoca R , Cinelli M , Matucci‐Cerinic M , Lapadula G . Bosentan regulates the expression of adhesion molecules on circulating T cells and serum soluble adhesion molecules in systemic sclerosis‐associated pulmonary arterial hypertension. AnnRheumDis 67: 1121‐1126, 2008.
 137. Ishikawa M , Cooper D , Arumugam TV , Zhang JH , Nanda A , Granger DN . Platelet‐leukocyte‐endothelial cell interactions after middle cerebral artery occlusion and reperfusion. JCerebBlood Flow Metab 24: 907‐915, 2004.
 138. Ishikawa M , Cooper D , Russell J , Salter JW , Zhang JH , Nanda A , Granger DN . Molecular determinants of the prothrombogenic and inflammatory phenotype assumed by the postischemic cerebral microcirculation. Stroke 34: 1777‐1782, 2003.
 139. Jaipersad AS , Lip GY , Silverman S , Shantsila E . The role of monocytes in angiogenesis and atherosclerosis. JAmCollCardiol 63: 1‐11, 2014.
 140. Janssen WJ , Barthel L , Muldrow A , Oberley‐Deegan RE , Kearns MT , Jakubzick C , Henson PM . Fas determines differential fates of resident and recruited macrophages during resolution of acute lung injury. Am J Respir Crit Care Med 184: 547‐560, 2011.
 141. Javaid K , Rahman A , Anwar KN , Frey RS , Minshall RD , Malik AB . Tumor necrosis factor‐alpha induces early‐onset endothelial adhesivity by protein kinase Czeta‐dependent activation of intercellular adhesion molecule‐1. Circ Res 92: 1089‐1097, 2003.
 142. Jean WC , Spellman SR , Nussbaum ES , Low WC . Reperfusion injury after focal cerebral ischemia: The role of inflammation and the therapeutic horizon. Neurosurgery 43: 1382‐1396, 1998.
 143. Jiang N , Chopp M , Chahwala S . Neutrophil inhibitory factor treatment of focal cerebral ischemia in the rat. Brain Res 788: 25‐34, 1998.
 144. Johansson PI , Stensballe J , Rasmussen LS , Ostrowski SR . A high admission syndecan‐1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg 254: 194‐200, 2011.
 145. Johnson RC , Chapman SM , Dong ZM , Ordovas JM , Mayadas TN , Herz J , Hynes RO , Schaefer EJ , Wagner DD . Absence of P‐selectin delays fatty streak formation in mice. JClinInvest 99: 1037‐1043, 1997.
 146. Jung U , Bullard DC , Tedder TF , Ley K . Velocity differences between L‐ and P‐selectin‐dependent neutrophil rolling in venules of mouse cremaster muscle in vivo. Am J Physiol 271: H2740‐H2747, 1996.
 147. Kataoka H , Kim SW , Plesnila N . Leukocyte‐endothelium interactions during permanent focal cerebral ischemia in mice. JCerebBlood Flow Metab 24: 668‐676, 2004.
 148. Kato GJ , Martyr S , Blackwelder WC , Nichols JS , Coles WA , Hunter LA , Brennan ML , Hazen SL , Gladwin MT . Levels of soluble endothelium‐derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality. BrJHaematol 130: 943‐953, 2005.
 149. Kawamura A , Miura S , Murayama T , Iwata A , Nishikawa H , Matsuo Y , Tsuchiya Y , Matsuo K , Tsuji E , Saku K . Changes in the expression of leukocyte adhesion molecules throughout the acute phase of myocardial infarction. J Atheroscler Thromb 11: 29‐34, 2004.
 150. Kay JM , Gillund TD , Heath D . Mast cells in the lungs of rats fed on Crotalaria spectabilis seeds. Am J Pathol 51: 1031‐1044, 1967.
 151. Kay JM , Waymire JC , Grover RF . Lung mast cell hyperplasia and pulmonary histamine‐forming capacity in hypoxic rats. Am J Physiol 226: 178‐184, 1974.
 152. Kerr KM , Auger WR , Marsh JJ , Comito RM , Fedullo RL , Smits GJ , Kapelanski DP , Fedullo PF , Channick RN , Jamieson SW , Moser KM . The use of cylexin (CY‐1503) in prevention of reperfusion lung injury in patients undergoing pulmonary thromboendarterectomy. Am J Respir Crit Care Med 162: 14‐20, 2000.
 153. Khan AI , Kerfoot SM , Heit B , Liu L , Andonegui G , Ruffell B , Johnson P , Kubes P . Role of CD44 and hyaluronan in neutrophil recruitment. J Immunol 173: 7594‐7601, 2004.
 154. Kherbeck N , Tamby MC , Bussone G , Dib H , Perros F , Humbert M , Mouthon L . The role of inflammation and autoimmunity in the pathophysiology of pulmonary arterial hypertension. ClinRevAllergy Immunol 44: 31‐38, 2013.
 155. Kiefmann R , Rifkind JM , Nagababu E , Bhattacharya J . Red blood cells induce hypoxic lung inflammation. Blood 111: 5205‐5214, 2008.
 156. Kim JS , Chopp M , Chen H , Levine SR , Carey JL , Welch KM . Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. JNeurolSci 128: 45‐50, 1995.
 157. Kimura N , Mitsuoka C , Kanamori A , Hiraiwa N , Uchimura K , Muramatsu T , Tamatani T , Kansas GS , Kannagi R . Reconstitution of functional L‐selectin ligands on a cultured human endothelial cell line by cotransfection of alpha1–>3 fucosyltransferase VII and newly cloned GlcNAcbeta:6‐sulfotransferase cDNA. Proc Natl Acad Sci U S A 96: 4530‐4535, 1999.
 158. King PD , Sandberg ET , Selvakumar A , Fang P , Beaudet AL , Dupont B . Novel isoforms of murine intercellular adhesion molecule‐1 generated by alternative RNA splicing. J Immunol 154: 6080‐6093, 1995.
 159. Kivi E , Elima K , Aalto K , Nymalm Y , Auvinen K , Koivunen E , Otto DM , Crocker PR , Salminen TA , Salmi M , Jalkanen S . Human Siglec‐10 can bind to vascular adhesion protein‐1 and serves as its substrate. Blood 114: 5385‐5392, 2009.
 160. Kleinschnitz C , Kraft P , Dreykluft A , Hagedorn I , Gobel K , Schuhmann MK , Langhauser F , Helluy X , Schwarz T , Bittner S , Mayer CT , Brede M , Varallyay C , Pham M , Bendszus M , Jakob P , Magnus T , Meuth SG , Iwakura Y , Zernecke A , Sparwasser T , Nieswandt B , Stoll G , Wiendl H . Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood 121: 679‐691, 2013.
 161. Klings ES , Anton BD , Rosenman D , Princeton S , Odhiambo A , Li G , Bernard SA , Steinberg MH , Farber HW . Pulmonary arterial hypertension and left‐sided heart disease in sickle cell disease: Clinical characteristics and association with soluble adhesion molecule expression. AmJHematol 83: 547‐553, 2008.
 162. Kobayashi M , Mitoma J , Nakamura N , Katsuyama T , Nakayama J , Fukuda M . Induction of peripheral lymph node addressin in human gastric mucosa infected by Helicobacter pylori. Proc Natl Acad Sci U S A 101: 17807‐17812, 2004.
 163. Kochanek PM , Hallenbeck JM . Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23: 1367‐1379, 1992.
 164. Koenen RR , Pruessmeyer J , Soehnlein O , Fraemohs L , Zernecke A , Schwarz N , Reiss K , Sarabi A , Lindbom L , Hackeng TM , Weber C , Ludwig A . Regulated release and functional modulation of junctional adhesion molecule A by disintegrin metalloproteinases. Blood 113: 4799‐4809, 2009.
 165. Kollert F , Christoph S , Probst C , Budweiser S , Bannert B , Binder M , Sehnert B , Voll RE , Warnatz K , Zissel G , Walker UA , Prasse A , Saalbach A . Soluble CD90 as a potential marker of pulmonary involvement in systemic sclerosis. Arthritis Care Res(Hoboken) 65: 281‐287, 2013.
 166. Krams M , Lees KR , Hacke W , Grieve AP , Orgogozo JM , Ford GA . Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN): An adaptive dose‐response study of UK‐279,276 in acute ischemic stroke. Stroke 34: 2543‐2548, 2003.
 167. Krupinski J , Kaluza J , Kumar P , Kumar S , Wang JM . Role of angiogenesis in patients with cerebral ischemic stroke. Stroke 25: 1794‐1798, 1994.
 168. Kubo H , Doyle NA , Graham L , Bhagwan SD , Quinlan WM , Doerschuk CM . L‐ and P‐selectin and CD11/CD18 in intracapillary neutrophil sequestration in rabbit lungs. Am J Respir Crit Care Med 159: 267‐274, 1999.
 169. Kuebler WM . Inflammatory pathways and microvascular responses in the lung. Pharmacol Rep 57(Suppl): 196‐205, 2005.
 170. Kuebler WM , Borges J , Sckell A , Kuhnle GE , Bergh K , Messmer K , Goetz AE . Role of L‐selectin in leukocyte sequestration in lung capillaries in a rabbit model of endotoxemia. AmJRespirCrit Care Med 161: 36‐43, 2000.
 171. Kuebler WM , Kuhnle GE , Groh J , Goetz AE . Contribution of selectins to leucocyte sequestration in pulmonary microvessels by intravital microscopy in rabbits. JPhysiol 501(Pt 2): 375‐386, 1997.
 172. Kuebler WM , Kuhnle GE , Groh J , Goetz AE . Leukocyte kinetics in pulmonary microcirculation: Intravital fluorescence microscopic study. JApplPhysiol (1985) 76: 65‐71, 1994.
 173. Kuebler WM , Ying X , Singh B , Issekutz AC , Bhattacharya J . Pressure is proinflammatory in lung venular capillaries. JClinInvest 104: 495‐502, 1999.
 174. Kumar S , Xu J , Kumar RS , Lakshmikanthan S , Kapur R , Kofron M , Chrzanowska‐Wodnicka M , Filippi MD . The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. J Exp Med 211: 1741‐1758, 2014.
 175. Kutlar A , Embury SH . Cellular adhesion and the endothelium: P‐selectin. Hematol Oncol Clin North Am 28: 323‐339, 2014.
 176. Kwak BR , Veillard N , Pelli G , Mulhaupt F , James RW , Chanson M , Mach F . Reduced connexin43 expression inhibits atherosclerotic lesion formation in low‐density lipoprotein receptor‐deficient mice. Circulation 107: 1033‐1039, 2003.
 177. Kypta RM , Waxman J . Wnt/beta‐catenin signalling in prostate cancer. Nat Rev Urol 9: 418‐428, 2012.
 178. Lakshmi SP , Reddy AT , Naik MU , Naik UP , Reddy RC . Effects of JAM‐A deficiency or blocking antibodies on neutrophil migration and lung injury in a murine model of ALI. Am J Physiol Lung Cell Mol Physiol 303: L758‐L766, 2012.
 179. Lamagna C , Meda P , Mandicourt G , Brown J , Gilbert RJ , Jones EY , Kiefer F , Ruga P , Imhof BA , Aurrand‐Lions M . Dual interaction of JAM‐C with JAM‐B and alpha(M)beta2 integrin: Function in junctional complexes and leukocyte adhesion. Mol Biol Cell 16: 4992‐5003, 2005.
 180. Langer HF , Daub K , Braun G , Schonberger T , May AE , Schaller M , Stein GM , Stellos K , Bueltmann A , Siegel‐Axel D , Wendel HP , Aebert H , Roecken M , Seizer P , Santoso S , Wesselborg S , Brossart P , Gawaz M . Platelets recruit human dendritic cells via Mac‐1/JAM‐C interaction and modulate dendritic cell function in vitro. ArteriosclerThrombVascBiol 27: 1463‐1470, 2007.
 181. Lapa M , Acencio MM , Farias AQ , Teixeira LR , Fernandes CJ , Jardim CP , Terra‐Filho M . Selectins and platelet‐derived growth factor (PDGF) in schistosomiasis‐associated pulmonary hypertension. Lung 192: 981‐986, 2014.
 182. Lasky LA , Singer MS , Dowbenko D , Imai Y , Henzel WJ , Grimley C , Fennie C , Gillett N , Watson SR , Rosen SD . An endothelial ligand for L‐selectin is a novel mucin‐like molecule. Cell 69: 927‐938, 1992.
 183. Lee WL , Downey GP . Neutrophil activation and acute lung injury. Curr Opin Crit Care 7: 1‐7, 2001.
 184. Lee WL , Slutsky AS . Sepsis and endothelial permeability. N Engl J Med 363: 689‐691, 2010.
 185. Lemaire LC , de Kruif MD , Giebelen IA , van Zoelen MA , van't Veer C , van der Poll T . Differential dose‐dependent effects of prednisolone on shedding of endothelial adhesion molecules during human endotoxemia. Immunol Lett 121: 93‐96, 2008.
 186. Leonardi S , Tricoci P , Mahaffey KW . Promises of PAR‐1 inhibition in acute coronary syndrome. Curr Cardiol Rep 14: 32‐39, 2012.
 187. Lever R , Rose MJ , McKenzie EA , Page CP . Heparanase induces inflammatory cell recruitment in vivo by promoting adhesion to vascular endothelium. Am J Physiol Cell Physiol 306: C1184‐C1190, 2014.
 188. Ley K , Laudanna C , Cybulsky MI , Nourshargh S . Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nat Rev Immunol 7: 678‐689, 2007.
 189. Liddington RC . Structural aspects of integrins. Adv Exp Med Biol 819: 111‐126, 2014.
 190. Lien WH , Klezovitch O , Vasioukhin V . Cadherin‐catenin proteins in vertebrate development. Curr Opin Cell Biol 18: 499‐506, 2006.
 191. Liesz A , Suri‐Payer E , Veltkamp C , Doerr H , Sommer C , Rivest S , Giese T , Veltkamp R . Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. NatMed 15: 192‐199, 2009.
 192. Lillehoj EP , Kato K , Lu W , Kim KC . Cellular and molecular biology of airway mucins. Int Rev Cell Mol Biol 303: 139‐202, 2013.
 193. Lindsberg PJ , Carpen O , Paetau A , Karjalainen‐Lindsberg ML , Kaste M . Endothelial ICAM‐1 expression associated with inflammatory cell response in human ischemic stroke. Circulation 94: 939‐945, 1996.
 194. Ling S , Nheu L , Komesaroff PA . Cell adhesion molecules as pharmaceutical target in atherosclerosis. MiniRevMedChem 12: 175‐183, 2012.
 195. Lipowsky HH . Protease activity and the role of the Endothelial glycocalyx in inflammation. Drug Discov Today Dis Models 8: 57‐62, 2011.
 196. Lipowsky HH . The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng 40: 840‐848, 2012.
 197. Love S , Barber R . Expression of P‐selectin and intercellular adhesion molecule‐1 in human brain after focal infarction or cardiac arrest. NeuropatholApplNeurobiol 27: 465‐473, 2001.
 198. Luft JH . Fine structures of capillary and endocapillary layer as revealed by ruthenium red. Fed Proc 25: 1773‐1783, 1966.
 199. Luhn K , Wild MK , Eckhardt M , Gerardy‐Schahn R , Vestweber D . The gene defective in leukocyte adhesion deficiency II encodes a putative GDP‐fucose transporter. Nat Genet 28: 69‐72, 2001.
 200. Luissint AC , Lutz PG , Calderwood DA , Couraud PO , Bourdoulous S . JAM‐L‐mediated leukocyte adhesion to endothelial cells is regulated in cis by alpha4beta1 integrin activation. J Cell Biol 183: 1159‐1173, 2008.
 201. Luissint AC , Nusrat A , Parkos CA . JAM‐related proteins in mucosal homeostasis and inflammation. Semin Immunopathol 36: 211‐226, 2014.
 202. Luo BH , Carman CV , Springer TA . Structural basis of integrin regulation and signaling. Annu Rev Immunol 25: 619‐647, 2007.
 203. Machlus KR , Italiano JE, Jr . The incredible journey: From megakaryocyte development to platelet formation. J Cell Biol 201: 785‐796, 2013.
 204. Madan M , Tcheng JE . Platelet Glycoprotein IIb/IIIa Integrin Blockade: Focus on Acute Myocardial Infarction. J Invasive Cardiol 10(Suppl A): 27A‐32A, 1998.
 205. Mahmoudi M , Delhaye C , Wakabayashi K , Torguson R , Xue Z , Suddath WO , Satler LF , Kent KM , Pichard AD , Waksman R . Integrilin in patients undergoing primary percutaneous coronary intervention for ST‐elevation myocardial infarction. J Interv Cardiol 24: 351‐356, 2011.
 206. Malawista SE , de Boisfleury Chevance A . Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes (PMN) in the presence of EDTA: PMN in close quarters require neither leukocyte integrins nor external divalent cations. Proc Natl Acad Sci U S A 94: 11577‐11582, 1997.
 207. Malech HL , Hickstein DD . Genetics, biology and clinical management of myeloid cell primary immune deficiencies: Chronic granulomatous disease and leukocyte adhesion deficiency. Curr Opin Hematol 14: 29‐36, 2007.
 208. Mamdouh Z , Chen X , Pierini LM , Maxfield FR , Muller WA . Targeted recycling of PECAM from endothelial surface‐connected compartments during diapedesis. Nature 421: 748‐753, 2003.
 209. Mamdouh Z , Kreitzer GE , Muller WA . Leukocyte transmigration requires kinesin‐mediated microtubule‐dependent membrane trafficking from the lateral border recycling compartment. J Exp Med 205: 951‐966, 2008.
 210. Mamdouh Z , Mikhailov A , Muller WA . Transcellular migration of leukocytes is mediated by the endothelial lateral border recycling compartment. J Exp Med 206: 2795‐2808, 2009.
 211. Manso AM , Kang SM , Ross RS . Integrins, focal adhesions, and cardiac fibroblasts. J Investig Med 57: 856‐860, 2009.
 212. Margadant C , Monsuur HN , Norman JC , Sonnenberg A . Mechanisms of integrin activation and trafficking. Curr Opin Cell Biol 23: 607‐614, 2011.
 213. Marmon S , Cammer M , Raine CS , Lisanti MP . Transcellular migration of neutrophils is a quantitatively significant pathway across dermal microvascular endothelial cells. Exp Dermatol 18: 88‐90, 2009.
 214. Marmon S , Hinchey J , Oh P , Cammer M , de Almeida CJ , Gunther L , Raine CS , Lisanti MP . Caveolin‐1 expression determines the route of neutrophil extravasation through skin microvasculature. Am J Pathol 174: 684‐692, 2009.
 215. Martin‐Padura I , Lostaglio S , Schneemann M , Williams L , Romano M , Fruscella P , Panzeri C , Stoppacciaro A , Ruco L , Villa A , Simmons D , Dejana E . Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. JCell Biol 142: 117‐127, 1998.
 216. Martinelli R , Zeiger AS , Whitfield M , Sciuto TE , Dvorak A , Van Vliet KJ , Greenwood J , Carman CV . Probing the biomechanical contribution of the endothelium to lymphocyte migration: Diapedesis by the path of least resistance. J Cell Sci 127: 3720‐3734, 2014.
 217. Massberg S , Brand K , Gruner S , Page S , Muller E , Muller I , Bergmeier W , Richter T , Lorenz M , Konrad I , Nieswandt B , Gawaz M . A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. JExpMed 196: 887‐896, 2002.
 218. Massberg S , Schurzinger K , Lorenz M , Konrad I , Schulz C , Plesnila N , Kennerknecht E , Rudelius M , Sauer S , Braun S , Kremmer E , Emambokus NR , Frampton J , Gawaz M . Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression and focal cerebral ischemia: An in vivo study in mice lacking glycoprotein IIb. Circulation 112: 1180‐1188, 2005.
 219. Massena S , Christoffersson G , Hjertstrom E , Zcharia E , Vlodavsky I , Ausmees N , Rolny C , Li JP , Phillipson M . A chemotactic gradient sequestered on endothelial heparan sulfate induces directional intraluminal crawling of neutrophils. Blood 116: 1924‐1931, 2010.
 220. Matsuo Y , Onodera H , Shiga Y , Nakamura M , Ninomiya M , Kihara T , Kogure K . Correlation between myeloperoxidase‐quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25: 1469‐1475, 1994.
 221. Matthay MA , Ware LB , Zimmerman GA . The acute respiratory distress syndrome. J Clin Invest 122: 2731‐2740, 2012.
 222. Mayr FB , Firbas C , Leitner JM , Spiel AO , Reiter RA , Beyer D , Meyer M , Wolff G , Jilma B . Effects of the pan‐selectin antagonist bimosiamose (TBC1269) in experimental human endotoxemia. Shock 29: 475‐482, 2008.
 223. McDonald B , McAvoy EF , Lam F , Gill V , de la Motte C , Savani RC , Kubes P . Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. J Exp Med 205: 915‐927, 2008.
 224. McEver RP . Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 14: 581‐586, 2002.
 225. McLaughlin F , Hayes BP , Horgan CM , Beesley JE , Campbell CJ , Randi AM . Tumor necrosis factor (TNF)‐alpha and interleukin (IL)‐1beta down‐regulate intercellular adhesion molecule (ICAM)‐2 expression on the endothelium. Cell Adhes Commun 6: 381‐400, 1998.
 226. McMillan SJ , Sharma RS , McKenzie EJ , Richards HE , Zhang J , Prescott A , Crocker PR . Siglec‐E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b beta2‐integrin‐dependent signaling. Blood 121: 2084‐2094, 2013.
 227. Mendel I , Yacov N , Harats D , Breitbart E . Therapies targeting innate immunity for fighting inflammation in atherosclerosis. CurrPharmDes 21: 1185‐1195, 2015.
 228. Millan J , Hewlett L , Glyn M , Toomre D , Clark P , Ridley AJ . Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM‐1 to caveola‐ and F‐actin‐rich domains. Nat Cell Biol 8: 113‐123, 2006.
 229. Millan J , Ridley AJ . Rho GTPases and leucocyte‐induced endothelial remodelling. Biochem J 385: 329‐337, 2005.
 230. Minamino T , Christou H , Hsieh CM , Liu Y , Dhawan V , Abraham NG , Perrella MA , Mitsialis SA , Kourembanas S . Targeted expression of heme oxygenase‐1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci U S A 98: 8798‐8803, 2001.
 231. Mitani Y , Ueda M , Maruyama K , Shimpo H , Kojima A , Matsumura M , Aoki K , Sakurai M . Mast cell chymase in pulmonary hypertension. Thorax 54: 88‐90, 1999.
 232. Mitroulis I , Alexaki VI , Kourtzelis I , Ziogas A , Hajishengallis G , Chavakis T . Leukocyte integrins: Role in leukocyte recruitment and as therapeutic targets in inflammatory disease. Pharmacol Ther 147: 123‐135, 2014.
 233. Miyata M , Sakuma F , Yoshimura A , Ishikawa H , Nishimaki T , Kasukawa R . Pulmonary hypertension in rats. 1. Role of bromodeoxyuridine‐positive mononuclear cells and alveolar macrophages. IntArchAllergy Immunol 108: 281‐286, 1995.
 234. Mizgerd JP . Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs. Semin Immunol 14: 123‐132, 2002.
 235. Mizgerd JP , Horwitz BH , Quillen HC , Scott ML , Doerschuk CM . Effects of CD18 deficiency on the emigration of murine neutrophils during pneumonia. J Immunol 163: 995‐999, 1999.
 236. Mizgerd JP , Meek BB , Kutkoski GJ , Bullard DC , Beaudet AL , Doerschuk CM . Selectins and neutrophil traffic: Margination and Streptococcus pneumoniae‐induced emigration in murine lungs. J Exp Med 184: 639‐645, 1996.
 237. Mizuno S , Farkas L , Al HA , Farkas D , Gomez‐Arroyo J , Kraskauskas D , Nicolls MR , Cool CD , Bogaard HJ , Voelkel NF . Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization. Am J Respir Cell MolBiol 47: 679‐687, 2012.
 238. Mocco J , Choudhri T , Huang J , Harfeldt E , Efros L , Klingbeil C , Vexler V , Hall W , Zhang Y , Mack W , Popilskis S , Pinsky DJ , Connolly ES, Jr . HuEP5C7 as a humanized monoclonal anti‐E/P‐selectin neurovascular protective strategy in a blinded placebo‐controlled trial of nonhuman primate stroke. CircRes 91: 907‐914, 2002.
 239. Motosugi H , Quinlan WM , Bree M , Doerschuk CM . Role of CD11b in focal acid‐induced pneumonia and contralateral lung injury in rats. Am J Respir Crit Care Med 157: 192‐198, 1998.
 240. Mulivor AW , Lipowsky HH . Inhibition of glycan shedding and leukocyte‐endothelial adhesion in postcapillary venules by suppression of matrix metalloprotease activity with doxycycline. Microcirculation 16: 657‐666, 2009.
 241. Mulivor AW , Lipowsky HH . Role of glycocalyx in leukocyte‐endothelial cell adhesion. Am J Physiol Heart Circ Physiol 283: H1282‐H1291, 2002.
 242. Muller AM , Cronen C , Muller KM , Kirkpatrick CJ . Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS. J Pathol 198: 270‐275, 2002.
 243. Muller WA . Leukocyte‐endothelial‐cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 24: 327‐334, 2003.
 244. Muller WA . Mechanisms of leukocyte transendothelial migration. Annu Rev Pathol 6: 323‐344, 2011.
 245. Mulligan MS , Miyasaka M , Tamatani T , Jones ML , Ward PA . Requirements for L‐selectin in neutrophil‐mediated lung injury in rats. J Immunol 152: 832‐840, 1994.
 246. Mulligan MS , Watson SR , Fennie C , Ward PA . Protective effects of selectin chimeras in neutrophil‐mediated lung injury. J Immunol 151: 6410‐6417, 1993.
 247. Muniz‐Lozano A , Rollini F , Franchi F , Angiolillo DJ . Update on platelet glycoprotein IIb/IIIa inhibitors: Recommendations for clinical practice. Ther Adv Cardiovasc Dis 7: 197‐213, 2013.
 248. Murai T , Sougawa N , Kawashima H , Yamaguchi K , Miyasaka M . CD44‐chondroitin sulfate interactions mediate leukocyte rolling under physiological flow conditions. Immunol Lett 93: 163‐170, 2004.
 249. Na SY , Mracsko E , Liesz A , Hunig T , Veltkamp R . Amplification of regulatory T cells using a CD28 superagonist reduces brain damage after ischemic stroke in mice. Stroke 46: 212‐220, 2015.
 250. Nageh MF , Sandberg ET , Marotti KR , Lin AH , Melchior EP , Bullard DC , Beaudet AL . Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol 17: 1517‐1520, 1997.
 251. Naik MU , Stalker TJ , Brass LF , Naik UP . JAM‐A protects from thrombosis by suppressing integrin alphaIIbbeta3‐dependent outside‐in signaling in platelets. Blood 119: 3352‐3360, 2012.
 252. Nakahata N . Thromboxane A2: Physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 118: 18‐35, 2008.
 253. Negrini D , Passi A , Moriondo A . The role of proteoglycans in pulmonary edema development. Intensive Care Med 34: 610‐618, 2008.
 254. Nekrasova O , Green KJ . Desmosome assembly and dynamics. Trends Cell Biol 23: 537‐546, 2013.
 255. Nelson A , Berkestedt I , Bodelsson M . Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand 58: 36‐43, 2014.
 256. Nelson A , Berkestedt I , Schmidtchen A , Ljunggren L , Bodelsson M . Increased levels of glycosaminoglycans during septic shock: Relation to mortality and the antibacterial actions of plasma. Shock 30: 623‐627, 2008.
 257. Nicolls MR , Taraseviciene‐Stewart L , Rai PR , Badesch DB , Voelkel NF . Autoimmunity and pulmonary hypertension: A perspective. EurRespirJ 26: 1110‐1118, 2005.
 258. Nieminen J , St‐Pierre C , Bhaumik P , Poirier F , Sato S . Role of galectin‐3 in leukocyte recruitment in a murine model of lung infection by Streptococcus pneumoniae. J Immunol 180: 2466‐2473, 2008.
 259. Nieminen M , Henttinen T , Merinen M , Marttila‐Ichihara F , Eriksson JE , Jalkanen S . Vimentin function in lymphocyte adhesion and transcellular migration. Nat Cell Biol 8: 156‐162, 2006.
 260. Nieswandt B , Pleines I , Bender M . Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J Thromb Thrombolysis 9(Suppl 1): 92‐104, 2011.
 261. Nieuwdorp M , Meuwese MC , Mooij HL , van Lieshout MH , Hayden A , Levi M , Meijers JC , Ince C , Kastelein JJ , Vink H , Stroes ES . Tumor necrosis factor‐alpha inhibition protects against endotoxin‐induced endothelial glycocalyx perturbation. Atherosclerosis 202: 296‐303, 2009.
 262. Nitschke L , Floyd H , Ferguson DJ , Crocker PR . Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22‐dependent homing of recirculating B cells. J Exp Med 189: 1513‐1518, 1999.
 263. Norman KE , Moore KL , McEver RP , Ley K . Leukocyte rolling in vivo is mediated by P‐selectin glycoprotein ligand‐1. Blood 86: 4417‐4421, 1995.
 264. Nottebaum AF , Cagna G , Winderlich M , Gamp AC , Linnepe R , Polaschegg C , Filippova K , Lyck R , Engelhardt B , Kamenyeva O , Bixel MG , Butz S , Vestweber D . VE‐PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE‐cadherin by leukocytes and by VEGF. J Exp Med 205: 2929‐2945, 2008.
 265. Nourshargh S , Krombach F , Dejana E . The role of JAM‐A and PECAM‐1 in modulating leukocyte infiltration in inflamed and ischemic tissues. J Leukoc Biol 80: 714‐718, 2006.
 266. O'Keefe TL , Williams GT , Davies SL , Neuberger MS . Hyperresponsive B cells in CD22‐deficient mice. Science 274: 798‐801, 1996.
 267. Oguz MM , Oguz AD , Sanli C , Cevik A . Serum levels of soluble ICAM‐1 in children with pulmonary artery hypertension. TexHeart InstJ 41: 159‐164, 2014.
 268. Ohman EM , Kleiman NS , Gacioch G , Worley SJ , Navetta FI , Talley JD , Anderson HV , Ellis SG , Cohen MD , Spriggs D , Miller M , Kereiakes D , Yakubov S , Kitt MM , Sigmon KN , Califf RM , Krucoff MW , Topol EJ . Combined accelerated tissue‐plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo‐controlled, dose‐ranging trial. IMPACT‐AMI Investigators. Circulation 95: 846‐854, 1997.
 269. Okajima K , Harada N , Sakurai G , Soga Y , Suga H , Terada T , Nakagawa T . Rapid assay for plasma soluble E‐selectin predicts the development of acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. Transl Res 148: 295‐300, 2006.
 270. Ostermann G , Weber KS , Zernecke A , Schroder A , Weber C . JAM‐1 is a ligand of the β2 integrin LFA‐1 involved in transendothelial migration of leukocytes. NatImmunol 3: 151‐158, 2002.
 271. Ozaki Y , Imanishi T , Teraguchi I , Nishiguchi T , Orii M , Shiono Y , Shimamura K , Ishibashi K , Tanimoto T , Yamano T , Ino Y , Yamaguchi T , Kubo T , Akasaka T . Association between P‐selectin glycoprotein ligand‐1 and pathogenesis in acute coronary syndrome assessed by optical coherence tomography. Atherosclerosis 233: 697‐703, 2014.
 272. Pablos JL , Santiago B , Tsay D , Singer MS , Palao G , Galindo M , Rosen SD . A HEV‐restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin‐alpha/beta and TNF‐alpha in cultured endothelial cells. BMC Immunol 6: 6, 2005.
 273. Pabst R , Tschernig T . Perivascular capillaries in the lung: An important but neglected vascular bed in immune reactions? J Allergy ClinImmunol 110: 209‐214, 2002.
 274. Parish CR . The role of heparan sulphate in inflammation. Nat Rev Immunol 6: 633‐643, 2006.
 275. Patel SS , Thiagarajan R , Willerson JT , Yeh ET . Inhibition of alpha4 integrin and ICAM‐1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE‐deficient mice. Circulation 97: 75‐81, 1998.
 276. Pelaseyed T , Bergstrom JH , Gustafsson JK , Ermund A , Birchenough GM , Schutte A , van der Post S , Svensson F , Rodriguez‐Pineiro AM , Nystrom EE , Wising C , Johansson ME , Hansson GC . The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev 260: 8‐20, 2014.
 277. Perros F , Dorfmuller P , Montani D , Hammad H , Waelput W , Girerd B , Raymond N , Mercier O , Mussot S , Cohen‐Kaminsky S , Humbert M , Lambrecht BN . Pulmonary lymphoid neogenesis in idiopathic pulmonary arterial hypertension. AmJRespirCrit Care Med 185: 311‐321, 2012.
 278. Perros F , Dorfmuller P , Souza R , Durand‐Gasselin I , Mussot S , Mazmanian M , Herve P , Emilie D , Simonneau G , Humbert M . Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. EurRespir J 29: 462‐468, 2007.
 279. Phillipson M , Heit B , Colarusso P , Liu L , Ballantyne CM , Kubes P . Intraluminal crawling of neutrophils to emigration sites: A molecularly distinct process from adhesion in the recruitment cascade. J Exp Med 203: 2569‐2575, 2006.
 280. Phillipson M , Kaur J , Colarusso P , Ballantyne CM , Kubes P . Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration. PLoS One 3: e1649, 2008.
 281. Pillai S , Netravali IA , Cariappa A , Mattoo H . Siglecs and immune regulation. Annu Rev Immunol 30: 357‐392, 2012.
 282. Pinto RF , Higuchi ML , Aiello VD . Decreased numbers of T‐lymphocytes and predominance of recently recruited macrophages in the walls of peripheral pulmonary arteries from 26 patients with pulmonary hypertension secondary to congenital cardiac shunts. CardiovascPathol 13: 268‐275, 2004.
 283. Pollard T. Cell Biology. Philadelphia, PA: Saunders/Elsevier, 2008.
 284. Potter DR , Damiano ER . The hydrodynamically relevant endothelial cell glycocalyx observed in vivo is absent in vitro. Circ Res 102: 770‐776, 2008.
 285. Potter DR , Jiang J , Damiano ER . The recovery time course of the endothelial cell glycocalyx in vivo and its implications in vitro. Circ Res 104: 1318‐1325, 2009.
 286. Pozzilli C , Lenzi GL , Argentino C , Carolei A , Rasura M , Signore A , Bozzao L , Pozzilli P . Imaging of leukocytic infiltration in human cerebral infarcts. Stroke 16: 251‐255, 1985.
 287. Prentice RL , Szatrowski TP , Kato H , Mason MW . Leukocyte counts and cerebrovascular disease. JChronicDis 35: 703‐714, 1982.
 288. Prestigiacomo CJ , Kim SC , Connolly ES, Jr. , Liao H , Yan SF , Pinsky DJ . CD18‐mediated neutrophil recruitment contributes to the pathogenesis of reperfused but not nonreperfused stroke. Stroke 30: 1110‐1117, 1999.
 289. Price LC , Wort SJ , Perros F , Dorfmuller P , Huertas A , Montani D , Cohen‐Kaminsky S , Humbert M . Inflammation in pulmonary arterial hypertension. Chest 141: 210‐221, 2012.
 290. Pries AR , Kuebler WM . Normal endothelium. Handb Exp Pharmacol 176 Pt. 1: 1‐40, 2006.
 291. Pullamsetti SS , Savai R , Janssen W , Dahal BK , Seeger W , Grimminger F , Ghofrani HA , Weissmann N , Schermuly RT . Inflammation, immunological reaction and role of infection in pulmonary hypertension. ClinMicrobiolInfect 17: 7‐14, 2011.
 292. Quinn KL , Henriques M , Tabuchi A , Han B , Yang H , Cheng WE , Tole S , Yu H , Luo A , Charbonney E , Tullis E , Lazarus A , Robinson LA , Ni H , Peterson BR , Kuebler WM , Slutsky AS , Zhang H . Human neutrophil peptides mediate endothelial‐monocyte interaction, foam cell formation, and platelet activation. ArteriosclerThrombVascBiol 31: 2070‐2079, 2011.
 293. Ren X , Akiyoshi K , Vandenbark AA , Hurn PD , Offner H . CD4+FoxP3+ regulatory T‐cells in cerebral ischemic stroke. Metab Brain Dis 26: 87‐90, 2011.
 294. Ritter LS , Orozco JA , Coull BM , McDonagh PF , Rosenblum WI . Leukocyte accumulation and hemodynamic changes in the cerebral microcirculation during early reperfusion after stroke. Stroke 31: 1153‐1161, 2000.
 295. Roberts W , Michno A , Aburima A , Naseem KM . Nitric oxide inhibits von Willebrand factor‐mediated platelet adhesion and spreading through regulation of integrin alpha(IIb)beta(3) and myosin light chain. J Thromb Thrombolysis 7: 2106‐2115, 2009.
 296. Rose DM , Alon R , Ginsberg MH . Integrin modulation and signaling in leukocyte adhesion and migration. Immunol Rev 218: 126‐134, 2007.
 297. Ross TD , Coon BG , Yun S , Baeyens N , Tanaka K , Ouyang M , Schwartz MA . Integrins in mechanotransduction. Curr Opin Cell Biol 25: 613‐618, 2013.
 298. Rouleau L , Rossi J , Leask RL . The response of human aortic endothelial cells in a stenotic hemodynamic environment: Effect of duration, magnitude, and spatial gradients in wall shear stress. JBiomechEng 132: 071015, 2010.
 299. Rubio‐Gayosso I , Platts SH , Duling BR . Reactive oxygen species mediate modification of glycocalyx during ischemia‐reperfusion injury. Am J Physiol Heart Circ Physiol 290: H2247‐H2256, 2006.
 300. Ruchaud‐Sparagano MH , Drost EM , Donnelly SC , Bird MI , Haslett C , Dransfield I . Potential pro‐inflammatory effects of soluble E‐selectin upon neutrophil function. Eur J Immunol 28: 80‐89, 1998.
 301. Rudick RA , Stuart WH , Calabresi PA , Confavreux C , Galetta SL , Radue EW , Lublin FD , Weinstock‐Guttman B , Wynn DR , Lynn F , Panzara MA , Sandrock AW , Investigators S . Natalizumab plus interferon beta‐1a for relapsing multiple sclerosis. N Engl J Med 354: 911‐923, 2006.
 302. Russell J , Cooper D , Tailor A , Stokes KY , Granger DN . Low venular shear rates promote leukocyte‐dependent recruitment of adherent platelets. AmJPhysiol GastrointestLiver Physiol 284: G123‐G129, 2003.
 303. Sakamaki F , Kyotani S , Nagaya N , Sato N , Oya H , Satoh T , Nakanishi N . Increased plasma P‐selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation 102: 2720‐2725, 2000.
 304. Sallisalmi M , Tenhunen J , Yang R , Oksala N , Pettila V . Vascular adhesion protein‐1 and syndecan‐1 in septic shock. Acta Anaesthesiol Scand 56: 316‐322, 2012.
 305. Salmon AH , Ferguson JK , Burford JL , Gevorgyan H , Nakano D , Harper SJ , Bates DO , Peti‐Peterdi J . Loss of the endothelial glycocalyx links albuminuria and vascular dysfunction. J Am Soc Nephrol 23: 1339‐1350, 2012.
 306. Santizo R , Pelligrino DA . Estrogen reduces leukocyte adhesion in the cerebral circulation of female rats. JCerebBlood Flow Metab 19: 1061‐1065, 1999.
 307. Sarada S , Himadri P , Mishra C , Geetali P , Ram MS , Ilavazhagan G . Role of oxidative stress and NFκB in hypoxia‐induced pulmonary edema. ExpBiolMed(Maywood) 233: 1088‐1098, 2008.
 308. Sato S , Ouellet N , Pelletier I , Simard M , Rancourt A , Bergeron MG . Role of galectin‐3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol 168: 1813‐1822, 2002.
 309. Savai R , Pullamsetti SS , Kolbe J , Bieniek E , Voswinckel R , Fink L , Scheed A , Ritter C , Dahal BK , Vater A , Klussmann S , Ghofrani HA , Weissmann N , Klepetko W , Banat GA , Seeger W , Grimminger F , Schermuly RT . Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. AmJRespirCrit Care Med 186: 897‐908, 2012.
 310. Schmidt EP , Lee WL , Zemans RL , Yamashita C , Downey GP . On, around, and through: Neutrophil‐endothelial interactions in innate immunity. Physiology 26: 334‐347, 2011.
 311. Schmidt EP , Li G , Li L , Fu L , Yang Y , Overdier KH , Douglas IS , Linhardt RJ . The circulating glycosaminoglycan signature of respiratory failure in critically ill adults. J Biol Chem 289: 8194‐8202, 2014.
 312. Schmidt EP , Yang Y , Janssen WJ , Gandjeva A , Perez MJ , Barthel L , Zemans RL , Bowman JC , Koyanagi DE , Yunt ZX , Smith LP , Cheng SS , Overdier KH , Thompson KR , Geraci MW , Douglas IS , Pearse DB , Tuder RM . The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 18: 1217‐1223, 2012.
 313. Schnoor M , Lai FP , Zarbock A , Klaver R , Polaschegg C , Schulte D , Weich HA , Oelkers JM , Rottner K , Vestweber D . Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo. J Exp Med 208: 1721‐1735, 2011.
 314. Schuhmann MK , Kraft P , Stoll G , Lorenz K , Meuth SG , Wiendl H , Nieswandt B , Sparwasser T , Beyersdorf N , Kerkau T , Kleinschnitz C . CD28 superagonist‐mediated boost of regulatory T cells increases thrombo‐inflammation and ischemic neurodegeneration during the acute phase of experimental stroke. JCerebBlood Flow Metab 35: 6‐10, 2015.
 315. Schumacher VA , Schlotzer‐Schrehardt U , Karumanchi SA , Shi X , Zaia J , Jeruschke S , Zhang D , Pavenstadt H , Drenckhan A , Amann K , Ng C , Hartwig S , Ng KH , Ho J , Kreidberg JA , Taglienti M , Royer‐Pokora B , Ai X . WT1‐dependent sulfatase expression maintains the normal glomerular filtration barrier. J Am Soc Nephrol 22: 1286‐1296, 2011.
 316. Scott DW , Patel RP . Endothelial heterogeneity and adhesion molecules N‐glycosylation: implications in leukocyte trafficking in inflammation. Glycobiology 23: 622‐633, 2013.
 317. Semenov AV , Kogan‐Ponomarev MI , Ruda MI , Komarov AL , Panchenko EP , Chazova IE , Mazurov AV . [Soluble P‐selectin ‐ a marker of platelet activation and vessel wall injury: Increase of soluble P‐selectin in plasma of patients with myocardial infarction, massive atherosclerosis and primary pulmonary hypertension]. TerArkh 72: 15‐20, 2000.
 318. Severson EA , Lee WY , Capaldo CT , Nusrat A , Parkos CA . Junctional adhesion molecule A interacts with Afadin and PDZ‐GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell 20: 1916‐1925, 2009.
 319. Severson EA , Parkos CA . Structural determinants of Junctional Adhesion Molecule A (JAM‐A) function and mechanisms of intracellular signaling. Curr Opin Cell Biol 21: 701‐707, 2009.
 320. Shaw AS , Amrein KE , Hammond C , Stern DF , Sefton BM , Rose JK . The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino‐terminal domain. Cell 59: 627‐636, 1989.
 321. Shaw SK , Bamba PS , Perkins BN , Luscinskas FW . Real‐time imaging of vascular endothelial‐cadherin during leukocyte transmigration across endothelium. J Immunol 167: 2323‐2330, 2001.
 322. Shyu KG , Chang H , Lin CC . Serum levels of intercellular adhesion molecule‐1 and E‐selectin in patients with acute ischaemic stroke. JNeurol 244: 90‐93, 1997.
 323. Simon SI , Cherapanov V , Nadra I , Waddell TK , Seo SM , Wang Q , Doerschuk CM , Downey GP . Signaling functions of L‐selectin in neutrophils: Alterations in the cytoskeleton and colocalization with CD18. J Immunol 163: 2891‐2901, 1999.
 324. Simonneau G , Robbins IM , Beghetti M , Channick RN , Delcroix M , Denton CP , Elliott CG , Gaine SP , Gladwin MT , Jing ZC , Krowka MJ , Langleben D , Nakanishi N , Souza R . Updated clinical classification of pulmonary hypertension. JAmCollCardiol 54: S43‐S54, 2009.
 325. Sirianni FE , Chu FS , Walker DC . Human alveolar wall fibroblasts directly link epithelial type 2 cells to capillary endothelium. Am J Respir Crit Care Med 168: 1532‐1537, 2003.
 326. Smalley DM , Ley K . L‐selectin: mechanisms and physiological significance of ectodomain cleavage. J Cell Mol Med 9: 255‐266, 2005.
 327. Smith CW . 3. Adhesion molecules and receptors. J Allergy Clin Immunol 121: S375‐S379; quiz S414, 2008.
 328. Smith ML , Long DS , Damiano ER , Ley K . Near‐wall micro‐PIV reveals a hydrodynamically relevant endothelial surface layer in venules in vivo. Biophys J 85: 637‐645, 2003.
 329. Sobel RA , Mitchell ME , Fondren G . Intercellular adhesion molecule‐1 (ICAM‐1) in cellular immune reactions in the human central nervous system. AmJPathol 136: 1309‐1316, 1990.
 330. Sobey CG , Drummond GR . CEACAM1: An adhesion molecule that limits blood‐brain barrier damage by neutrophils after stroke. Circ Res 113: 952‐953, 2013.
 331. Song Y , Coleman L , Shi J , Beppu H , Sato K , Walsh K , Loscalzo J , Zhang YY . Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2‐mutant mice. Am J Physiol Heart CircPhysiol 295: H677‐H690, 2008.
 332. Soriano SG , Coxon A , Wang YF , Frosch MP , Lipton SA , Hickey PR , Mayadas TN . Mice deficient in Mac‐1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 30: 134‐139, 1999.
 333. Soriano SG , Wang YF , Wagner DD , Frenette PS . P‐ and E‐selectin‐deficient mice are susceptible to cerebral ischemia‐reperfusion injury. Brain Res 835: 360‐364, 1999.
 334. Sorrentino S , Studt JD , Medalia O , Tanuj Sapra K . Roll, adhere, spread and contract: Structural mechanics of platelet function. Eur J Cell Biol 94: 129‐138, 2015.
 335. Sparrow CP , Burton CA , Hernandez M , Mundt S , Hassing H , Patel S , Rosa R , Hermanowski‐Vosatka A , Wang PR , Zhang D , Peterson L , Detmers PA , Chao YS , Wright SD . Simvastatin has anti‐inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. ArteriosclerThrombVascBiol 21: 115‐121, 2001.
 336. Sperandio M . Selectins and glycosyltransferases in leukocyte rolling in vivo. FEBS J 273: 4377‐4389, 2006.
 337. Springer TA . Adhesion receptors of the immune system. Nature 346: 425‐434, 1990.
 338. Springer TA . Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 76: 301‐314, 1994.
 339. Stanley P , Schachter H , Taniguchi N . N‐Glycans. In: Varki A , Cummings RD , Esko JD , Freeze HH , Stanley P , Bertozzi CR , Hart GW , Etzler ME , editors. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press, 2009, pp. 101‐114.
 340. Steinman L . Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab. Nat Rev Drug Discov 4: 510‐518, 2005.
 341. Steinman L . The discovery of natalizumab, a potent therapeutic for multiple sclerosis. J Cell Biol 199: 413‐416, 2012.
 342. Steppan J , Hofer S , Funke B , Brenner T , Henrich M , Martin E , Weitz J , Hofmann U , Weigand MA . Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix. J Surg Res 165: 136‐141, 2011.
 343. Sughrue ME , Mehra A , Connolly ES, Jr. , D'Ambrosio AL . Anti‐adhesion molecule strategies as potential neuroprotective agents in cerebral ischemia: A critical review of the literature. InflammRes 53: 497‐508, 2004.
 344. Sungprem K , Khongphatthanayothin A , Kiettisanpipop P , Chotivitayatarakorn P , Poovorawan Y , Lertsapcharoen P . Serum level of soluble intercellular adhesion molecule‐1 correlates with pulmonary arterial pressure in children with congenital heart disease. PediatrCardiol 30: 472‐476, 2009.
 345. Supanc V , Biloglav Z , Kes VB , Demarin V . Role of cell adhesion molecules in acute ischemic stroke. AnnSaudiMed 31: 365‐370, 2011.
 346. Suzawa K , Kobayashi M , Sakai Y , Hoshino H , Watanabe M , Harada O , Ohtani H , Fukuda M , Nakayama J . Preferential induction of peripheral lymph node addressin on high endothelial venule‐like vessels in the active phase of ulcerative colitis. Am J Gastroenterol 102: 1499‐1509, 2007.
 347. Suzuki H , Hayashi T , Tojo SJ , Kitagawa H , Kimura K , Mizugaki M , Itoyama Y , Abe K . Anti‐P‐selectin antibody attenuates rat brain ischemic injury. NeurosciLett 265: 163‐166, 1999.
 348. Swirski FK , Pittet MJ , Kircher MF , Aikawa E , Jaffer FA , Libby P , Weissleder R . Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease. Proc Natl Acad Sci U S A 103: 10340‐10345, 2006.
 349. Tabuchi A , Kuebler WM . Endothelium‐platelet interactions in inflammatory lung disease. VasculPharmacol 49: 141‐150, 2008.
 350. Tailor A , Cooper D , Granger DN . Platelet‐vessel wall interactions in the microcirculation. Microcirculation 12: 275‐285, 2005.
 351. Takeichi M . Dynamic contacts: Rearranging adherens junctions to drive epithelial remodelling. Nat Rev Mol Cell Biol 15: 397‐410, 2014.
 352. Takeshima R , Kirsch JR , Koehler RC , Gomoll AW , Traystman RJ . Monoclonal leukocyte antibody does not decrease the injury of transient focal cerebral ischemia in cats. Stroke 23: 247‐252, 1992.
 353. Taylor KR , Gallo RL . Glycosaminoglycans and their proteoglycans: Host‐associated molecular patterns for initiation and modulation of inflammation. FASEB J 20: 9‐22, 2006.
 354. Toppila S , Paavonen T , Laitinen A , Laitinen LA , Renkonen R . Endothelial sulfated sialyl Lewis x glycans, putative L‐selectin ligands, are preferentially expressed in bronchial asthma but not in other chronic inflammatory lung diseases. Am J Respir Cell Mol Biol 23: 492‐498, 2000.
 355. Tozzi CA , Thakker‐Varia S , Yu SY , Bannett RF , Peng BW , Poiani GJ , Wilson FJ , Riley DJ . Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat. Am J RespirCell MolBiol 18: 497‐510, 1998.
 356. Tu L , Delahunty MD , Ding H , Luscinskas FW , Tedder TF . The cutaneous lymphocyte antigen is an essential component of the L‐selectin ligand induced on human vascular endothelial cells. J Exp Med 189: 241‐252, 1999.
 357. Tucker A , McMurtry IF , Alexander AF , Reeves JT , Grover RF . Lung mast cell density and distribution in chronically hypoxic animals. J ApplPhysiol 42: 174‐178, 1977.
 358. Tuder RM , Groves B , Badesch DB , Voelkel NF . Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 144: 275‐285, 1994.
 359. Uhl E , Beck J , Stummer W , Lehmberg J , Baethmann A . Leukocyte‐endothelium interactions in pial venules during the early and late reperfusion period after global cerebral ischemia in gerbils. JCerebBlood Flow Metab 20: 979‐987, 2000.
 360. Ulich TR , Howard SC , Remick DG , Yi ES , Collins T , Guo K , Yin S , Keene JL , Schmuke JJ , Steininger CN , et al. Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E‐selectin expression; anti‐E‐selectin and soluble E‐selectin inhibit acute inflammation. Inflammation 18: 389‐398, 1994.
 361. van Buul JD , Allingham MJ , Samson T , Meller J , Boulter E , Garcia‐Mata R , Burridge K . RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans‐endothelial migration. J Cell Biol 178: 1279‐1293, 2007.
 362. van den Berg BM , Nieuwdorp M , Stroes ES , Vink H . Glycocalyx and endothelial (dys) function: From mice to men. Pharmacol Rep 58 Suppl: 75‐80, 2006.
 363. van Roy F . Beyond E‐cadherin: Roles of other cadherin superfamily members in cancer. Nat Rev Cancer 14: 121‐134, 2014.
 364. Varki A , Crocker PR . I‐type Lectins. In: Varki A , Cummings RD , Esko JD , Freeze HH , Stanley P , Bertozzi CR , Hart GW , Etzler ME , editors. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press, 2009, pp. 459‐474.
 365. Varki A , Etzler ME , Cummings RD , Esko JD . Discovery and classification of glycan‐binding proteins. In: Varki A , Cummings RD , Esko JD , Freeze HH , Stanley P , Bertozzi CR , Hart GW , Etzler ME , editors. Essentials of Glycobiology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press, 2009, pp. 375‐386.
 366. Vestweber D . Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium. Immunol Rev 218: 178‐196, 2007.
 367. Vestweber D , Winderlich M , Cagna G , Nottebaum AF . Cell adhesion dynamics at endothelial junctions: VE‐cadherin as a major player. Trends Cell Biol 19: 8‐15, 2009.
 368. Vink H , Duling BR . Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ Res 79: 581‐589, 1996.
 369. Voelkel NF , Tuder RM . Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension. Eur Respir J 8: 2129‐2138, 1995.
 370. Voisin MB , Woodfin A , Nourshargh S . Monocytes and neutrophils exhibit both distinct and common mechanisms in penetrating the vascular basement membrane in vivo. Arterioscler Thromb Vasc Biol 29: 1193‐1199, 2009.
 371. von Andrian UH , Chambers JD , McEvoy LM , Bargatze RF , Arfors KE , Butcher EC . Two‐step model of leukocyte‐endothelial cell interaction in inflammation: Distinct roles for LECAM‐1 and the leukocyte beta 2 integrins in vivo. Proc Natl Acad Sci U S A 88: 7538‐7542, 1991.
 372. Vuorte J , Lindsberg PJ , Kaste M , Meri S , Jansson SE , Rothlein R , Repo H . Anti‐ICAM‐1 monoclonal antibody R6.5 (Enlimomab) promotes activation of neutrophils in whole blood. JImmunol 162: 2353‐2357, 1999.
 373. Waddell TK , Fialkow L , Chan CK , Kishimoto TK , Downey GP . Signaling functions of L‐selectin. Enhancement of tyrosine phosphorylation and activation of MAP kinase. J Biol Chem 270: 15403‐15411, 1995.
 374. Walker DC , Behzad AR , Chu F . Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia. Microvasc Res 50: 397‐416, 1995.
 375. Wang L , Fuster M , Sriramarao P , Esko JD . Endothelial heparan sulfate deficiency impairs L‐selectin‐ and chemokine‐mediated neutrophil trafficking during inflammatory responses. Nat Immunol 6: 902‐910, 2005.
 376. Wang S , Voisin MB , Larbi KY , Dangerfield J , Scheiermann C , Tran M , Maxwell PH , Sorokin L , Nourshargh S . Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils. J Exp Med 203: 1519‐1532, 2006.
 377. Wang Y , Zhang AC , Ni Z , Herrera A , Walcheck B . ADAM17 activity and other mechanisms of soluble L‐selectin production during death receptor‐induced leukocyte apoptosis. J Immunol 184: 4447‐4454, 2010.
 378. Weber C , Zernecke A , Libby P . The multifaceted contributions of leukocyte subsets to atherosclerosis: Lessons from mouse models. NatRevImmunol 8: 802‐815, 2008.
 379. Weber DA , Sumagin R , McCall IC , Leoni G , Neumann PA , Andargachew R , Brazil JC , Medina‐Contreras O , Denning TL , Nusrat A , Parkos CA . Neutrophil‐derived JAML inhibits repair of intestinal epithelial injury during acute inflammation. Mucosal Immunol 7: 1221‐1232, 2014.
 380. Wedepohl S , Beceren‐Braun F , Riese S , Buscher K , Enders S , Bernhard G , Kilian K , Blanchard V , Dernedde J , Tauber R . L‐selectin–a dynamic regulator of leukocyte migration. Eur J Cell Biol 91: 257‐264, 2012.
 381. Wei YS , Liu YG , Huang RY , Tang RG , Meng LQ . [Intercellular adhesion molecule‐1 gene K469E polymorphism and genetic susceptibility of ischemic stroke in Chinese Zhuang populations]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 22: 305‐308, 2005.
 382. Weinbaum S , Tarbell JM , Damiano ER . The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng 9: 121‐167, 2007.
 383. Wenzel K , Felix S , Kleber FX , Brachold R , Menke T , Schattke S , Schulte KL , Glaser C , Rohde K , Baumann G , . E‐selectin polymorphism and atherosclerosis: An association study. HumMolGenet 3: 1935‐1937, 1994.
 384. Wessel F , Winderlich M , Holm M , Frye M , Rivera‐Galdos R , Vockel M , Linnepe R , Ipe U , Stadtmann A , Zarbock A , Nottebaum AF , Vestweber D . Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE‐cadherin. Nat Immunol 15: 223‐230, 2014.
 385. Whittall C , Kehoe O , King S , Rot A , Patterson A , Middleton J . A chemokine self‐presentation mechanism involving formation of endothelial surface microstructures. J Immunol 190: 1725‐1736, 2013.
 386. Wiesinger A , Peters W , Chappell D , Kentrup D , Reuter S , Pavenstadt H , Oberleithner H , Kumpers P . Nanomechanics of the endothelial glycocalyx in experimental sepsis. PLoS One 8: e80905, 2013.
 387. Williams A , Heath D , Kay JM , Smith P . Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery. Thorax 32: 287‐295, 1977.
 388. Williams AE , Chambers RC . The mercurial nature of neutrophils: Still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol 306: L217‐L230, 2014.
 389. Wolburg H , Wolburg‐Buchholz K , Engelhardt B . Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol 109: 181‐190, 2005.
 390. Woodfin A , Reichel CA , Khandoga A , Corada M , Voisin MB , Scheiermann C , Haskard DO , Dejana E , Krombach F , Nourshargh S . JAM‐A mediates neutrophil transmigration in a stimulus‐specific manner in vivo: Evidence for sequential roles for JAM‐A and PECAM‐1 in neutrophil transmigration. Blood 110: 1848‐1856, 2007.
 391. Woodfin A , Voisin MB , Imhof BA , Dejana E , Engelhardt B , Nourshargh S . Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM‐2, JAM‐A, and PECAM‐1. Blood 113: 6246‐6257, 2009.
 392. Woodfin A , Voisin MB , Nourshargh S . Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17: 9‐17, 2010.
 393. Worthen GS , Schwab B, III , Elson EL , Downey GP . Mechanics of stimulated neutrophils: Cell stiffening induces retention in capillaries. Science 245: 183‐186, 1989.
 394. Worthington JJ , Klementowicz JE , Travis MA . TGFbeta: A sleeping giant awoken by integrins. Trends Biochem Sci 36: 47‐54, 2011.
 395. Wu G , Li F , Li P , Ruan C . Detection of plasma alpha‐granule membrane protein GMP‐140 using radiolabeled monoclonal antibodies in thrombotic diseases. Haemostasis 23: 121‐128, 1993.
 396. Xu D , Esko JD . Demystifying heparan sulfate‐protein interactions. Annu Rev Biochem 83: 129‐157, 2014.
 397. Yagmur E , Koch A , Haumann M , Kramann R , Trautwein C , Tacke F . Hyaluronan serum concentrations are elevated in critically ill patients and associated with disease severity. Clin Biochem 45: 82‐87, 2012.
 398. Yago T , Zarnitsyna VI , Klopocki AG , McEver RP , Zhu C . Transport governs flow‐enhanced cell tethering through L‐selectin at threshold shear. Biophys J 92: 330‐342, 2007.
 399. Yamagishi S , Imaizumi T . Pericyte biology and diseases. Int J Tissue React 27: 125‐135, 2005.
 400. Yan J , Read SJ , Henderson RD , Hull R , O'Sullivan JD , McCombe PA , Greer JM . Frequency and function of regulatory T cells after ischaemic stroke in humans. JNeuroimmunol 243: 89‐94, 2012.
 401. Yang L , Froio RM , Sciuto TE , Dvorak AM , Alon R , Luscinskas FW . ICAM‐1 regulates neutrophil adhesion and transcellular migration of TNF‐alpha‐activated vascular endothelium under flow. Blood 106: 584‐592, 2005.
 402. Yang Y , Yang G , Schmidt EP . In vivo measurement of the mouse pulmonary endothelial surface layer. J Vis Exp e50322, 2013.
 403. Yaoita N , Shirakawa R , Fukumoto Y , Sugimura K , Miyata S , Miura Y , Nochioka K , Miura M , Tatebe S , Aoki T , Yamamoto S , Satoh K , Kimura T , Shimokawa H , Horiuchi H . Platelets are highly activated in patients of chronic thromboembolic pulmonary hypertension. ArteriosclerThrombVascBiol 34: 2486‐2494, 2014.
 404. Yednock TA , Cannon C , Fritz LC , Sanchez‐Madrid F , Steinman L , Karin N . Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356: 63‐66, 1992.
 405. Yenari MA , Kunis D , Sun GH , Onley D , Watson L , Turner S , Whitaker S , Steinberg GK . Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. ExpNeurol 153: 223‐233, 1998.
 406. Yenari MA , Sun GH , Kunis DM , Onley D , Vexler V . L‐selectin inhibition does not reduce injury in a rabbit model of transient focal cerebral ischemia. NeurolRes 23: 72‐78, 2001.
 407. Yilmaz G , Arumugam TV , Stokes KY , Granger DN . Role of T lymphocytes and interferon‐gamma in ischemic stroke. Circulation 113: 2105‐2112, 2006.
 408. Yilmaz G , Granger DN . Cell adhesion molecules and ischemic stroke. NeurolRes 30: 783‐793, 2008.
 409. Yonekawa K , Harlan JM . Targeting leukocyte integrins in human diseases. J Leukoc Biol 77: 129‐140, 2005.
 410. Zahler S , Hoffmann A , Gloe T , Pohl U . Gap‐junctional coupling between neutrophils and endothelial cells: A novel modulator of transendothelial migration. JLeukocBiol 73: 118‐126, 2003.
 411. Zanette EM , Roberti C , Mancini G , Pozzilli C , Bragoni M , Toni D . Spontaneous middle cerebral artery reperfusion in ischemic stroke. A follow‐up study with transcranial Doppler. Stroke 26: 430‐433, 1995.
 412. Zarbock A , Ley K . Mechanisms and consequences of neutrophil interaction with the endothelium. Am J Pathol 172: 1‐7, 2008.
 413. Zarbock A , Ley K , McEver RP , Hidalgo A . Leukocyte ligands for endothelial selectins: Specialized glycoconjugates that mediate rolling and signaling under flow. Blood 118: 6743‐6751, 2011.
 414. Zeller JA , Lenz A , Eschenfelder CC , Zunker P , Deuschl G . Platelet‐leukocyte interaction and platelet activation in acute stroke with and without preceding infection. Arterioscler Thromb Vasc Biol 25: 1519‐1523, 2005.
 415. Zemans RL , Colgan SP , Downey GP . Transepithelial migration of neutrophils: Mechanisms and implications for acute lung injury. Am J Respir Cell Mol Biol 40: 519‐535, 2009.
 416. Zernecke A , Liehn EA , Fraemohs L , von HP , Koenen RR , Corada M , Dejana E , Weber C . Importance of junctional adhesion molecule‐A for neointimal lesion formation and infiltration in atherosclerosis‐prone mice. ArteriosclerThrombVascBiol 26: e10‐e13, 2006.
 417. Zhang L , Zhang ZG , Zhang RL , Lu M , Krams M , Chopp M . Effects of a selective CD11b/CD18 antagonist and recombinant human tissue plasminogen activator treatment alone and in combination in a rat embolic model of stroke. Stroke 34: 1790‐1795, 2003.
 418. Zhang RL , Chopp M , Jiang N , Tang WX , Prostak J , Manning AM , Anderson DC . Anti‐intercellular adhesion molecule‐1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke 26: 1438‐1442, 1995.
 419. Zuberi RI , Ge XN , Jiang S , Bahaie NS , Kang BN , Hosseinkhani RM , Frenzel EM , Fuster MM , Esko JD , Rao SP , Sriramarao P . Deficiency of endothelial heparan sulfates attenuates allergic airway inflammation. J Immunol 183: 3971‐3979, 2009.

Related Articles:

Pulmonary Vascular Disease
Systemic Hypertension

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Adhesion Molecules: Master Controllers of the Circulatory System
 

How to Cite

Eric P. Schmidt, Wolfgang M. Kuebler, Warren L. Lee, Gregory P. Downey. Adhesion Molecules: Master Controllers of the Circulatory System. Compr Physiol 2016, null: 945-973. doi: 10.1002/cphy.c150020