Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Platelets and Their Interactions with Other Immune Cells

Fong W. Lam, K. Vinod Vijayan, Rolando E. Rumbaut

10.1002/cphy.c140074

Source: Volume 5, Issue 3, July 2015

Published online: June 2015

Full Article on Wiley Online Library



ABSTRACT

Platelets are anucleate blood cells, long known to be critically involved in hemostasis and thrombosis. In addition to their role in blood clots, increasing evidence reveals significant roles for platelets in inflammation and immunity. However, the notion that platelets represent immune cells is not broadly recognized in the field of Physiology. This article reviews the role of platelets in inflammation and immune responses, and highlights their interactions with other immune cells, including examples of major functional consequences of these interactions. Published 2015. Compr Physiol 5:1265‐1280, 2015.

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. (A) Platelets localize to the site of injury, binding to fibrin, and forming a hemostatic plug. (B) Electron micrograph of activated platelets, which spread out over an injured area and extend filopodia. Reprinted, with permission, from Macmillan Publishers Ltd: Nature Materials (59), 2010.
Figure 2. Figure 2. Ultrastructural features of a discoid platelet showing α‐granules, mitochondrion, the marginal microtubule band, and open canicular system. Reprinted, with permission, from Macmillan Publishers Ltd: Nature Reviews Immunology (182), 2011.
Figure 3. Figure 3. Examples of adhesive interactions between platelets (red) and leukocytes (blue). Platelets contain a number of integrins and cell adhesion molecules on their surface which bind to both leukocytes and endothelial cells (green). Major cell adhesion molecule interactions include (platelet‐leukocyte) P‐selectin‐PSGL‐1 and GP1bα‐Mac‐1. Platelets also adhere to endothelial cells and help capture flowing leukocytes from the circulation. Reprinted from reference (85) with permission from Wiley.
Figure 4. Figure 4. Adhesive interactions between activated platelets and neutrophils. (A) EM image of an inflamed mouse cremaster venule, demonstrating platelet‐neutrophil‐endothelial cell interaction. Image courtesy of Dr. Alan Burns, University of Houston College of Optometry. (B) Platelet (red)‐neutrophil (green/blue) interactions in suspension after platelet activation.
Figure 5. Figure 5. Selected examples of proinflammatory effects of platelets resulting in functional consequences on leukocytes. Platelets interact with leukocytes through both adhesive mechanisms as well as release of cytokines/chemokines. This results in leukocyte activation and enhanced leukocyte‐endothelial adhesion. Through these mechanisms, platelets participate in several normal and pathologic immune functions including microbial killing, leukocyte homing, wound healing, allergic inflammation, and atherosclerosis, among others.


Figure 1. (A) Platelets localize to the site of injury, binding to fibrin, and forming a hemostatic plug. (B) Electron micrograph of activated platelets, which spread out over an injured area and extend filopodia. Reprinted, with permission, from Macmillan Publishers Ltd: Nature Materials (59), 2010.


Figure 2. Ultrastructural features of a discoid platelet showing α‐granules, mitochondrion, the marginal microtubule band, and open canicular system. Reprinted, with permission, from Macmillan Publishers Ltd: Nature Reviews Immunology (182), 2011.


Figure 3. Examples of adhesive interactions between platelets (red) and leukocytes (blue). Platelets contain a number of integrins and cell adhesion molecules on their surface which bind to both leukocytes and endothelial cells (green). Major cell adhesion molecule interactions include (platelet‐leukocyte) P‐selectin‐PSGL‐1 and GP1bα‐Mac‐1. Platelets also adhere to endothelial cells and help capture flowing leukocytes from the circulation. Reprinted from reference (85) with permission from Wiley.


Figure 4. Adhesive interactions between activated platelets and neutrophils. (A) EM image of an inflamed mouse cremaster venule, demonstrating platelet‐neutrophil‐endothelial cell interaction. Image courtesy of Dr. Alan Burns, University of Houston College of Optometry. (B) Platelet (red)‐neutrophil (green/blue) interactions in suspension after platelet activation.


Figure 5. Selected examples of proinflammatory effects of platelets resulting in functional consequences on leukocytes. Platelets interact with leukocytes through both adhesive mechanisms as well as release of cytokines/chemokines. This results in leukocyte activation and enhanced leukocyte‐endothelial adhesion. Through these mechanisms, platelets participate in several normal and pathologic immune functions including microbial killing, leukocyte homing, wound healing, allergic inflammation, and atherosclerosis, among others.
References
 1. Albelda SM , Smith CW , Ward PA . Adhesion molecules and inflammatory injury. FASEB J 8: 504‐512, 1994.
 2. Andonegui G , Kerfoot SM , McNagny K , Ebbert KVJ , Patel KD , Kubes P . Platelets express functional Toll‐like receptor‐4. Blood 106: 2417‐2423, 2005.
 3. Andrews RK , Gardiner EE , Shen Y , Whisstock JC , Berndt MC . Glycoprotein Ib‐IX‐V. Int J Biochem Cell Biol 35: 1170‐1174, 2003.
 4. Arai M , Yamamoto N , Moroi M , Akamatsu N , Fukutake K , Tanoue K . Platelets with 10% of the normal amount of glycoprotein VI have an impaired response to collagen that results in a mild bleeding tendency. Br J Haematol 89: 124‐130, 1995.
 5. Armitage RJ , Fanslow WC , Strockbine L , Sato TA , Clifford KN , Macduff BM , Anderson DM , Gimpel SD , Davis‐Smith T , Maliszewski CR . Molecular and biological characterization of a murine ligand for CD40. Nature 357: 80‐82, 1992.
 6. Asaduzzaman M , Lavasani S , Rahman M , Zhang S , Braun OÖ, Jeppsson B , Thorlacius H . Platelets support pulmonary recruitment of neutrophils in abdominal sepsis. Crit Care Med 37: 1389‐1396, 2009.
 7. Assoian RK , Sporn MB . Type beta transforming growth factor in human platelets: Release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 102: 1217‐1223, 1986.
 8. Ayyanathan K , Webbs TE , Sandhu AK , Athwal RS , Barnard EA , Kunapuli SP . Cloning and chromosomal localization of the human P2Y1 purinoceptor. Biochem Biophys Res Commun 218: 783‐788, 1996.
 9. Baltus T , Hundelshausen von P , Mause SF , Buhre W , Rossaint R , Weber C . Differential and additive effects of platelet‐derived chemokines on monocyte arrest on inflamed endothelium under flow conditions. J Leukoc Biol 78: 435‐441, 2005.
 10. Barrientos S , Stojadinovic O , Golinko MS , Brem H , Tomic‐Canic M . Growth factors and cytokines in wound healing. Wound Repair Regen 16: 585‐601, 2008.
 11. Beller DI , Springer TA , Schreiber RD . Anti‐Mac‐1 selectively inhibits the mouse and human type three complement receptor. J Exp Med 156: 1000‐1009, 1982.
 12. Bentfeld‐Barker ME , Bainton DF . Identification of primary lysosomes in human megakaryocytes and platelets. Blood 59: 472‐481, 1982.
 13. Benveniste J , Henson PM , Cochrane CG . Leukocyte‐dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet‐activating factor. J Exp Med 136: 1356‐1377, 1972.
 14. Berger M , Gray JA , Roth BL . The expanded biology of serotonin. Annu Rev Med 60: 355‐366, 2009.
 15. Berman CL , Yeo EL , Wencel‐Drake JD , Furie BC , Ginsberg MH , Furie B . A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation‐dependent granule‐external membrane protein. J Clin Invest 78: 130‐137, 1986.
 16. Bertozzi CC , Schmaier AA , Mericko P , Hess PR , Zou Z , Chen M , Chen C‐Y , Xu B , Lu M‐M , Zhou D , Sebzda E , Santore MT , Merianos DJ , Stadtfeld M , Flake AW , Graf T , Skoda R , Maltzman JS , Koretzky GA , Kahn ML . Platelets regulate lymphatic vascular development through CLEC‐2‐SLP‐76 signaling. Blood 116: 661‐670, 2010.
 17. Bizzozero G . Sur un nouvel élément morphologique du sang chez les mammifères et sur son importance dans la thrombose et dans la coagulation. Archives Italiennes de Biologie 1: 1‐4, 1882.
 18. Blair P , Flaumenhaft R . Platelet alpha‐granules: Basic biology and clinical correlates. Blood Rev 23: 177‐189, 2009.
 19. Blair P , Rex S , Vitseva O , Beaulieu L , Tanriverdi K , Chakrabarti S , Hayashi C , Genco CA , Iafrati M , Freedman JE . Stimulation of Toll‐like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3‐kinase. Circ Res 104: 346‐354, 2009.
 20. Boehlen F , Clemetson KJ . Platelet chemokines and their receptors: What is their relevance to platelet storage and transfusion practice? Transfus Med 11: 403‐417, 2001.
 21. Boilard E , Nigrovic PA , Larabee K , Watts GFM , Coblyn JS , Weinblatt ME , Massarotti EM , Remold‐O'Donnell E , Farndale RW , Ware J , Lee DM . Platelets amplify inflammation in arthritis via collagen‐dependent microparticle production. Science 327: 580‐583, 2010.
 22. Booyse FM , Rafelson ME . Stable messenger RNA in the synthesis of contractile protein in human platelets. Biochim Biophys Acta 145: 188‐190, 1967.
 23. Brandt E , Ludwig A , Petersen F , Flad HD . Platelet‐derived CXC chemokines: Old players in new games. Immunol Rev 177: 204‐216, 2000.
 24. Brandt E , Petersen F , Ludwig A , Ehlert JE , Bock L , Flad HD . The beta‐thromboglobulins and platelet factor 4: Blood platelet‐derived CXC chemokines with divergent roles in early neutrophil regulation. J Leukoc Biol 67: 471‐478, 2000.
 25. Brass LF , Tomaiuolo M , Stalker TJ . Harnessing the platelet signaling network to produce an optimal hemostatic response. Hematol Oncol Clin North Am 27: 381‐409, 2013.
 26. Brinkmann V , Reichard U , Goosmann C , Fauler B , Uhlemann Y , Weiss DS , Weinrauch Y , Zychlinsky A . Neutrophil extracellular traps kill bacteria. Science 303: 1532‐1535, 2004.
 27. Brown GT , McIntyre TM . Lipopolysaccharide signaling without a nucleus: Kinase cascades stimulate platelet shedding of proinflammatory IL‐1β‐rich microparticles. J Immunol 186: 5489‐5496, 2011.
 28. Bruemmer D , Riggers U , Holzmeister J , Grill M , Lippek F , Settmacher U , Regitz‐Zagrosek V , Fleck E , Graf K . Expression of CD40 in vascular smooth muscle cells and macrophages is associated with early development of human atherosclerotic lesions. Am J Cardiol 87: 21‐27, 2001.
 29. Burnouf T , Goubran HA , Chou M‐L , Devos D , Radosevic M . Platelet microparticles: Detection and assessment of their paradoxical functional roles in disease and regenerative medicine. Blood Rev 28: 155‐166, 2014.
 30. Burns AR , Bowden RA , Abe Y , Walker DC , Simon SI , Entman ML , Smith CW . P‐selectin mediates neutrophil adhesion to endothelial cell borders. J Leukoc Biol 65: 299‐306, 1999.
 31. Bussolino F , Fischer E , Turrini F , Kazatchkine MD , Arese P . Platelet‐activating factor enhances complement‐dependent phagocytosis of diamide‐treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1). J Biol Chem 264: 21711‐21719, 1989.
 32. Caudrillier A , Kessenbrock K , Gilliss BM , Nguyen JX , Marques MB , Monestier M , Toy P , Werb Z , Looney MR . Platelets induce neutrophil extracellular traps in transfusion‐related acute lung injury. J Clin Invest 122: 2661‐2671, 2012.
 33. Celik S , Langer H , Stellos K , May AE , Shankar V , Kurz K , Katus HA , Gawaz MP , Dengler TJ . Platelet‐associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium. Thromb Haemost 98: 798‐805, 2007.
 34. Chaipan C , Soilleux EJ , Simpson P , Hofmann H , Gramberg T , Marzi A , Geier M , Stewart EA , Eisemann J , Steinkasserer A , Suzuki‐Inoue K , Fuller GL , Pearce AC , Watson SP , Hoxie JA , Baribaud F , Pöhlmann S . DC‐SIGN and CLEC‐2 mediate human immunodeficiency virus type 1 capture by platelets. J Virol 80: 8951‐8960, 2006.
 35. Chan‐Yeung M , Lam S , Chan H , Tse KS , Salari H . The release of platelet‐activating factor into plasma during allergen‐induced bronchoconstriction. J Allergy Clin Immunol 87: 667‐673, 1991.
 36. Chang ZL . Important aspects of Toll‐like receptors, ligands and their signaling pathways. Inflamm Res 59: 791‐808, 2010.
 37. Chesney CM , Harper E , Colman RW . Human platelet collagenase. J Clin Invest 53: 1647‐1654, 1974.
 38. Clancy L , Freedman JE . New paradigms in thrombosis: Novel mediators and biomarkers platelet RNA transfer. J Thromb Thrombolysis 37: 12‐16, 2014.
 39. Clark RA , Klebanoff SJ . Neutrophil‐platelet interaction mediated by myeloperoxidase and hydrogen peroxide. J Immunol 124: 399‐405, 1980.
 40. Clark SR , Ma AC , Tavener SA , Mcdonald B , Goodarzi Z , Kelly MM , Patel KD , Chakrabarti S , Mcavoy E , Sinclair GD , Keys EM , Allen‐Vercoe E , Devinney R , Doig CJ , Green FHY , Kubes P . Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13: 463‐469, 2007.
 41. Clawson CC , White JG . Platelet interaction with bacteria. II. Fate of the bacteria. Am J Pathol 65: 381‐397, 1971.
 42. CLAY CB , JACKSON G . Anaphylactoid reaction with death following the injection treatment of varicose veins with sodium morrhuate. J Med Assoc Ga 44: 25, 1955.
 43. Cognasse F , Hamzeh H , Chavarin P , Acquart S , Genin C , Garraud O . Evidence of Toll‐like receptor molecules on human platelets. Immunol Cell Biol 83: 196‐198, 2005.
 44. Cognasse F , Hamzeh‐Cognasse H , Lafarge S , Chavarin P , Cogné M , Richard Y , Garraud O . Human platelets can activate peripheral blood B cells and increase production of immunoglobulins. Exp Hematol 35: 1376‐1387, 2007.
 45. Coller BS , Seligsohn U , West SM , Scudder LE , Norton KJ . Platelet fibrinogen and vitronectin in Glanzmann thrombasthenia: Evidence consistent with specific roles for glycoprotein IIb/IIIA and alpha v beta 3 integrins in platelet protein trafficking. Blood 78: 2603‐2610, 1991.
 46. Danese S , la Motte de C , Sturm A , Vogel JD , West GA , Strong SA , Katz JA , Fiocchi C . Platelets trigger a CD40‐dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 124: 1249‐1264, 2003.
 47. Dankert J , Krijgsveld J , van der Werff J , Joldersma W , Zaat SA . Platelet microbicidal activity is an important defense factor against viridans streptococcal endocarditis. J Infect Dis 184: 597‐605, 2001.
 48. Dasgupta SK , Abdel‐Monem H , Niravath P , Le A , Bellera RV , Langlois K , Nagata S , Rumbaut RE , Thiagarajan P . Lactadherin and clearance of platelet‐derived microvesicles. Blood 113: 1332‐1339, 2009.
 49. Davì G , Patrono C . Platelet activation and atherothrombosis. N Engl J Med 357: 2482‐2494, 2007.
 50. De Meyer SF , Suidan GL , Fuchs TA , Monestier M , Wagner DD . Extracellular chromatin is an important mediator of ischemic stroke in mice. Arterioscler Thromb Vasc Biol 32: 1884‐1891, 2012.
 51. Del Conde I , Cruz MA , Zhang H , López JA , Afshar‐Kharghan V . Platelet activation leads to activation and propagation of the complement system. J Exp Med 201: 871‐879, 2005.
 52. Diacovo TG , deFougerolles AR , Bainton DF , Springer TA . A functional integrin ligand on the surface of platelets: Intercellular adhesion molecule‐2. J Clin Invest 94: 1243‐1251, 1994.
 53. Dixon DA , Tolley ND , Bemis‐Standoli K , Martinez ML , Weyrich AS , Morrow JD , Prescott SM , Zimmerman GA . Expression of COX‐2 in platelet‐monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling. J Clin Invest 116: 2727‐2738, 2006.
 54. Donaldson DM , Roberts RR , Larsen HS , Tew JG . Interrelationship between serum beta‐lysin, lysozyme, and the antibody‐complement system in killing Escherichia coli. Infect Immun 10: 657‐666, 1974.
 55. Donaldson DM , Tew JG . beta‐Lysin of platelet origin. Bacteriol Rev 41: 501‐513, 1977.
 56. Dore M , Burns AR , Hughes BJ , Entman ML , Smith CW . Chemoattractant‐induced changes in surface expression and redistribution of a functional ligand for P‐selectin on neutrophils. Blood 87: 2029‐2037, 1996.
 57. Duerschmied D , Bode C , Ahrens I . Immune functions of platelets. Thromb Haemost 112: 678‐691, 2014.
 58. Duerschmied D , Suidan GL , Demers M , Herr N , Carbo C , Brill A , Cifuni SM , Mauler M , Cicko S , Bader M , Idzko M , Bode C , Wagner DD . Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice. Blood 121: 1008‐1015, 2013.
 59. Ehrlicher A , Hartwig JH . Cell mechanics: Contracting to stiffness. Nat Mater 10: 12‐13, 2011.
 60. Ekdahl KN , Nilsson B . Phosphorylation of complement component C3 and C3 fragments by a human platelet protein kinase. Inhibition of factor I‐mediated cleavage of C3b. J Immunol 154: 6502‐6510, 1995.
 61. Fava RA , Casey TT , Wilcox J , Pelton RW , Moses HL , Nanney LB . Synthesis of transforming growth factor‐beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha‐granules. Blood 76: 1946‐1955, 1990.
 62. Feingold DS , Goldman JN , Kuritz HM . Locus of the action of serum and the role of lysozyme in the serum bactericidal reaction. J Bacteriol 96: 2118‐2126, 1968.
 63. Fernandes LS , Conde ID , Wayne Smith C , Kansas GS , Snapp KR , Bennet N , Ballantyne C , McIntire LV , O'Brian Smith E , Klem JA , Mathew S , Frangogiannis N , Turner NA , Maresh KJ , Kleiman NS . Platelet‐monocyte complex formation: Effect of blocking PSGL‐1 alone, and in combination with alphaIIbbeta3 and alphaMbeta2, in coronary stenting. Thromb Res 111: 171‐177, 2003.
 64. Fowler VG , Sakoulas G , McIntyre LM , Meka VG , Arbeit RD , Cabell CH , Stryjewski ME , Eliopoulos GM , Reller LB , Corey GR , Jones T , Lucindo N , Yeaman MR , Bayer AS . Persistent bacteremia due to methicillin‐resistant Staphylococcus aureus infection is associated with agr dysfunction and low‐level in vitro resistance to thrombin‐induced platelet microbicidal protein. J Infect Dis 190: 1140‐1149, 2004.
 65. Fox JE , Aggerbeck LP , Berndt MC . Structure of the glycoprotein Ib.IX complex from platelet membranes. J Biol Chem 263: 4882‐4890, 1988.
 66. Foy TM , Aruffo A , Bajorath J , Buhlmann JE , Noelle RJ . Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 14: 591‐617, 1996.
 67. Fuchs TA , Abed U , Goosmann C , Hurwitz R , Schulze I , Wahn V , Weinrauch Y , Brinkmann V , Zychlinsky A . Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176: 231‐241, 2007.
 68. Fuchs TA , Bhandari AA , Wagner DD . Histones induce rapid and profound thrombocytopenia in mice. Blood 118: 3708‐3714, 2011.
 69. Fuchs TA , Brill A , Duerschmied D , Schatzberg D , Monestier M , Myers DD , Wrobleski SK , Wakefield TW , Hartwig JH , Wagner DD . Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A 107: 15880‐15885, 2010.
 70. Fukami MH . Isolation of dense granules from human platelets. Meth Enzymol 215: 36‐42, 1992.
 71. Garcia BA , Smalley DM , Cho H , Shabanowitz J , Ley K , Hunt DF . The platelet microparticle proteome. J Proteome Res 4: 1516‐1521, 2005.
 72. Gay NJ , Symmons MF , Gangloff M , Bryant CE . Assembly and localization of Toll‐like receptor signalling complexes. Nat Rev Immunol 14: 546‐558, 2014.
 73. Gear ARL , Camerini D . Platelet chemokines and chemokine receptors: Linking hemostasis, inflammation, and host defense. Microcirculation 10: 335‐350, 2003.
 74. Gidlöf O , van der Brug M , Ohman J , Gilje P , Olde B , Wahlestedt C , Erlinge D . Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 121: 3908‐17‐S1‐26, 2013.
 75. Gu M , Xi X , Englund GD , Berndt MC , Du X . Analysis of the roles of 14‐3‐3 in the platelet glycoprotein Ib‐IX‐mediated activation of integrin alpha(IIb)beta(3) using a reconstituted mammalian cell expression model. J Cell Biol 147: 1085‐1096, 1999.
 76. Habib A , FitzGerald GA , Maclouf J . Phosphorylation of the thromboxane receptor alpha, the predominant isoform expressed in human platelets. J Biol Chem 274: 2645‐2651, 1999.
 77. Halvorsen B , Smedbakken LM , Michelsen AE , Skjelland M , Bjerkeli V , Sagen EL , Taskén K , Bendz B , Gullestad L , Holm S , Biessen EA , Aukrust P . Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2‐related mechanisms and enhance the anti‐inflammatory effects of CXCL13. Atherosclerosis 234: 352‐359, 2014.
 78. Hamburger SA , McEver RP . GMP‐140 mediates adhesion of stimulated platelets to neutrophils. Blood 75: 550‐554, 1990.
 79. Hartwig H , Drechsler M , Lievens D , Kramp B , Hundelshausen von P , Lutgens E , Weber C , Döring Y , Soehnlein O . Platelet‐derived PF4 reduces neutrophil apoptosis following arterial occlusion. Thromb Haemost 111: 562‐564, 2014.
 80. Hasegawa S , Pawankar R , Suzuki K , Nakahata T , Furukawa S , Okumura K , Ra C . Functional expression of the high affinity receptor for IgE (FcepsilonRI) in human platelets and its' intracellular expression in human megakaryocytes. Blood 93: 2543‐2551, 1999.
 81. Hastings JW , Sailer M , Johnson K , Roy KL , Vederas JC , Stiles ME . Characterization of leucocin A‐UAL 187 and cloning of the bacteriocin gene from Leuconostoc gelidum. J Bacteriol 173: 7491‐7500, 1991.
 82. Hattori R , Hamilton KK , Fugate RD , McEver RP , Sims PJ . Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP‐140. J Biol Chem 264: 7768‐7771, 1989.
 83. Henn V , Slupsky JR , Gräfe M , Anagnostopoulos I , Förster R , Müller‐Berghaus G , Kroczek RA . CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391: 591‐594, 1998.
 84. Heo S‐K , Ju S‐A , Lee S‐C , Park S‐M , Choe S‐Y , Kwon B , Kwon BS , Kim B‐S . LIGHT enhances the bactericidal activity of human monocytes and neutrophils via HVEM. J Leukoc Biol 79: 330‐338, 2006.
 85. Herter JM , Rossaint J , Zarbock A . Platelets in inflammation and immunity. J Thromb Haemost 12: 1764‐1775, 2014.
 86. Herzberg MC , Brintzenhofe KL , Clawson CC . Aggregation of human platelets and adhesion of Streptococcus sanguis . Infect Immun 39: 1457‐1469, 1983.
 87. Hirsch JG . Comparative bactericidal activities of blood serum and plasma serum. J Exp Med 112: 15‐22, 1960.
 88. Holmsen H , Weiss HJ . Secretable storage pools in platelets. Annu Rev Med 30: 119‐134, 1979.
 89. Hottz ED , Lopes JF , Freitas C , Valls‐de‐Souza R , Oliveira MF , Bozza MT , Da Poian AT , Weyrich AS , Zimmerman GA , Bozza FA , Bozza PT . Platelets mediate increased endothelium permeability in dengue through NLRP3‐inflammasome activation. Blood 122: 3405‐3414, 2013.
 90. Hristov M , Zernecke A , Bidzhekov K , Liehn EA , Shagdarsuren E , Ludwig A , Weber C . Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res 100: 590‐597, 2007.
 91. Hundelshausen von P , Schmitt MMN. Platelets and their chemokines in atherosclerosis‐clinical applications. Front Physiol 5: 294, 2014.
 92. Hundelshausen von P , Weber KS , Huo Y , Proudfoot AE , Nelson PJ , Ley K , Weber C . RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 103: 1772‐1777, 2001.
 93. Isenberg WM , McEver RP , Shuman MA , Bainton DF . Topographic distribution of a granule membrane protein (GMP‐140) that is expressed on the platelet surface after activation: An immunogold‐surface replica study. Blood Cells 12: 191‐204, 1986.
 94. Ishihara H , Zeng D , Connolly AJ , Tam C , Coughlin SR . Antibodies to protease‐activated receptor 3 inhibit activation of mouse platelets by thrombin. Blood 91: 4152‐4157, 1998.
 95. Israels SJ , McMillan‐Ward EM . CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen. Thromb Haemost 93: 311‐318, 2005.
 96. Issekutz AC , Rowter D , Springer TA . Role of ICAM‐1 and ICAM‐2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration. J Leukoc Biol 65: 117‐126, 1999.
 97. Johnson CE , Belfield PW , Davis S , Cooke NJ , Spencer A , Davies JA . Platelet activation during exercise induced asthma: Effect of prophylaxis with cromoglycate and salbutamol. Thorax 41: 290‐294, 1986.
 98. Jones DH , Anderson DC , Burr BL , Rudloff HE , Smith CW , Krater SS , Schmalstieg FC . Quantitation of intracellular Mac‐1 (CD11b/CD18) pools in human neutrophils. J Leukoc Biol 44: 535‐544, 1988.
 99. Joseph M , Auriault C , Capron A , Vorng H , Viens P . A new function for platelets: IgE‐dependent killing of schistosomes. Nature 303: 810‐812, 1983.
 100. Jung C‐J , Yeh C‐Y , Shun C‐T , Hsu R‐B , Cheng H‐W , Lin C‐S , Chia J‐S . Platelets enhance biofilm formation and resistance of endocarditis‐inducing streptococci on the injured heart valve. J Infect Dis 205: 1066‐1075, 2012.
 101. Kahn ML , Nakanishi‐Matsui M , Shapiro MJ , Ishihara H , Coughlin SR . Protease‐activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103: 879‐887, 1999.
 102. Kameyoshi Y , Schröder JM , Christophers E , Yamamoto S . Identification of the cytokine RANTES released from platelets as an eosinophil chemotactic factor. Int Arch Allergy Immunol. 104(Suppl 1): 49‐51, 1994.
 103. Kasperska‐Zajac A , Rogala B . Markers of platelet activation in plasma of patients suffering from persistent allergic rhinitis with or without asthma symptoms. Clin Exp Allergy 35: 1462‐1465, 2005.
 104. Kato Y , Kaneko MK , Kunita A , Ito H , Kameyama A , Ogasawara S , Matsuura N , Hasegawa Y , Suzuki‐Inoue K , Inoue O , Ozaki Y , Narimatsu H . Molecular analysis of the pathophysiological binding of the platelet aggregation‐inducing factor podoplanin to the C‐type lectin‐like receptor CLEC‐2. Cancer Sci 99: 54‐61, 2008.
 105. Keane C , Tilley D , Cunningham A , Smolenski A , Kadioglu A , Cox D , Jenkinson HF , Kerrigan SW . Invasive Streptococcus pneumoniae trigger platelet activation via Toll‐like receptor 2. J Thromb Haemost 8: 2757‐2765, 2010.
 106. Kenney DM , Linck RW . The cystoskeleton of unstimulated blood platelets: Structure and composition of the isolated marginal microtubular band. J Cell Sci 78: 1‐22, 1985.
 107. Kerrigan AM , Navarro‐Nuñez L , Pyz E , Finney BA , Willment JA , Watson SP , Brown GD . Podoplanin‐expressing inflammatory macrophages activate murine platelets via CLEC‐2. J Thromb Haemost 10: 484‐486, 2012.
 108. Khan SY , Kelher MR , Heal JM , Blumberg N , Boshkov LK , Phipps R , Gettings KF , McLaughlin NJ , Silliman CC . Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion‐related acute lung injury. Blood 108: 2455‐2462, 2006.
 109. Kinoshita T , Medof ME , Silber R , Nussenzweig V . Distribution of decay‐accelerating factor in the peripheral blood of normal individuals and patients with paroxysmal nocturnal hemoglobinuria. J Exp Med 162: 75‐92, 1985.
 110. Kollef MH , Schuster DP . The acute respiratory distress syndrome. N Engl J Med 332: 27‐37, 1995.
 111. Koupenova M , Vitseva O , MacKay CR , Beaulieu LM , Benjamin EJ , Mick E , Kurt‐Jones EA , Ravid K , Freedman JE . Platelet‐TLR7 mediates host survival and platelet count during viral infection in the absence of platelet‐dependent thrombosis. Blood 124: 791‐802, 2014.
 112. Kraemer BF , Campbell RA , Schwertz H , Cody MJ , Franks Z , Tolley ND , Kahr WHA , Lindemann S , Seizer P , Yost CC , Zimmerman GA , Weyrich AS . Novel anti‐bacterial activities of β‐defensin 1 in human platelets: Suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog. 7: e1002355, 2011.
 113. Krijgsveld J , Zaat SA , Meeldijk J , van Veelen PA , Fang G , Poolman B , Brandt E , Ehlert JE , Kuijpers AJ , Engbers GH , Feijen J , Dankert J . Thrombocidins, microbicidal proteins from human blood platelets, are C‐terminal deletion products of CXC chemokines. J Biol Chem 275: 20374‐20381, 2000.
 114. Kuijper PH , Gallardo Torres HI , Lammers JW , Sixma JJ , Koenderman L , Zwaginga JJ . Platelet and fibrin deposition at the damaged vessel wall: Cooperative substrates for neutrophil adhesion under flow conditions. Blood 89: 166‐175, 1997.
 115. Kwakman PHS , Krijgsveld J , de Boer L , Nguyen LT , Boszhard L , Vreede J , Dekker HL , Speijer D , Drijfhout JW , Velde te AA , Crielaard W , Vogel HJ , Vandenbroucke‐Grauls CMJE , Zaat SAJ . Native thrombocidin‐1 and unfolded thrombocidin‐1 exert antimicrobial activity via distinct structural elements. J Biol Chem 286: 43506‐43514, 2011.
 116. Lam FW , Burns AR , Smith CW , Rumbaut RE . Platelets enhance neutrophil transendothelial migration via P‐selectin glycoprotein ligand‐1. Am J Physiol Heart Circ Physiol 300: H468‐H475, 2011.
 117. Lam FW , Cruz MA , Leung H‐CE , Parikh KS , Smith CW , Rumbaut RE . Histone induced platelet aggregation is inhibited by normal albumin. Thromb Res 132: 69‐76, 2013.
 118. Landry P , Plante I , Ouellet DL , Perron MP , Rousseau G , Provost P . Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 16: 961‐966, 2009.
 119. Langer HF , Choi EY , Zhou H , Schleicher R , Chung K‐J , Tang Z , Göbel K , Bdeir K , Chatzigeorgiou A , Wong C , Bhatia S , Kruhlak MJ , Rose JW , Burns JB , Hill KE , Qu H , Zhang Y , Lehrmann E , Becker KG , Wang Y , Simon DI , Nieswandt B , Lambris JD , Li X , Meuth SG , Kubes P , Chavakis T . Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis. Circ Res 110: 1202‐1210, 2012.
 120. Larsen E , Celi A , Gilbert GE , Furie BC , Erban JK , Bonfanti R , Wagner DD , Furie B . PADGEM protein: A receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 59: 305‐312, 1989.
 121. Lasagni L , Francalanci M , Annunziato F , Lazzeri E , Giannini S , Cosmi L , Sagrinati C , Mazzinghi B , Orlando C , Maggi E , Marra F , Romagnani S , Serio M , Romagnani P . An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP‐10, Mig, and I‐TAC, and acts as functional receptor for platelet factor 4. J Exp Med 197: 1537‐1549, 2003.
 122. Laszik Z , Jansen PJ , Cummings RD , Tedder TF , McEver RP , Moore KL . P‐selectin glycoprotein ligand‐1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells. Blood 88: 3010‐3021, 1996.
 123. Le Y , Zhou Y , Iribarren P , Wang J . Chemokines and chemokine receptors: Their manifold roles in homeostasis and disease. Cell Mol Immunol 1: 95‐104, 2004.
 124. Li P , Li M , Lindberg MR , Kennett MJ , Xiong N , Wang Y . PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med 207: 1853‐1862, 2010.
 125. Li Z , Delaney MK , O'Brien KA , Du X . Signaling during platelet adhesion and activation. Arterioscler Thromb Vasc Biol 30: 2341‐2349, 2010.
 126. Li Z , Rumbaut RE , Burns AR , Smith CW . Platelet response to corneal abrasion is necessary for acute inflammation and efficient re‐epithelialization. Invest Ophthalmol Vis Sci 47: 4794‐4802, 2006.
 127. Lievens D , Zernecke A , Seijkens T , Soehnlein O , Beckers L , Munnix ICA , Wijnands E , Goossens P , van Kruchten R , Thevissen L , Boon L , Flavell RA , Noelle RJ , Gerdes N , Biessen EA , Daemen MJAP , Heemskerk JWM , Weber C , Lutgens E . Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood 116: 4317‐4327, 2010.
 128. Lindemann S , Tolley ND , Dixon DA , McIntyre TM , Prescott SM , Zimmerman GA , Weyrich AS . Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 154: 485‐490, 2001.
 129. Linder BL , Chernoff A , Kaplan KL , Goodman DS . Release of platelet‐derived growth factor from human platelets by arachidonic acid. Proc Natl Acad Sci USA 76: 4107‐4111, 1979.
 130. Lukasik M , Rozalski M , Luzak B , Michalak M , Ambrosius W , Watala C , Kozubski W . Enhanced platelet‐derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients. Platelets 24: 63‐70, 2013.
 131. Luzzatto G , Cella G , Boschetto P , Fabbri L . Lack of increase or reduction in circulating platelet factor 4 and heparin‐releasable platelet factor 4 in symptomatic patients with asthma. J Lipid Mediat 7: 151‐154, 1993.
 132. Ma AC , Kubes P . Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost 6: 415‐420, 2008.
 133. Ma Y‐Q , Plow EF , Geng J‐G . P‐selectin binding to P‐selectin glycoprotein ligand‐1 induces an intermediate state of alphaMbeta2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils. Blood 104: 2549‐2556, 2004.
 134. Mannaioni PF , Di Bello MG , Masini E . Platelets and inflammation: Role of platelet‐derived growth factor, adhesion molecules and histamine. Inflamm Res 46: 4‐18, 1997.
 135. May AE , Langer H , Seizer P , Bigalke B , Lindemann S , Gawaz M . Platelet‐leukocyte interactions in inflammation and atherothrombosis. Semin Thromb Hemost 33: 123‐127, 2007.
 136. McEver RP , Martin MN . A monoclonal antibody to a membrane glycoprotein binds only to activated platelets. J Biol Chem 259: 9799‐9804, 1984.
 137. Mei J , Liu Y , Dai N , Favara M , Greene T , Jeyaseelan S , Poncz M , Lee JS , Worthen GS . CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity 33: 106‐117, 2010.
 138. Michelson AD , Loscalzo J , Melnick B , Coller BS , Handin RI . Partial characterization of a binding site for von Willebrand factor on glycocalicin. Blood 67: 19‐26, 1986.
 139. Moore KL , Patel KD , Bruehl RE , Li F , Johnson DA , Lichenstein HS , Cummings RD , Bainton DF , McEver RP . P‐selectin glycoprotein ligand‐1 mediates rolling of human neutrophils on P‐selectin. J Cell Biol 128: 661‐671, 1995.
 140. Moore KL , Stults NL , Diaz S , Smith DF , Cummings RD , Varki A , McEver RP . Identification of a specific glycoprotein ligand for P‐selectin (CD62) on myeloid cells. J Cell Biol 118: 445‐456, 1992.
 141. Moroi M , Jung SM , Okuma M , Shinmyozu K . A patient with platelets deficient in glycoprotein VI that lack both collagen‐induced aggregation and adhesion. J Clin Invest 84: 1440‐1445, 1989.
 142. Morowitz DA , Allen LW , Kirsner JB . Thrombocytosis in chronic inflammatory bowel disease. Ann Intern Med 68: 1013‐1021, 1968.
 143. Morrison JF , Pearson SB , Dean HG , Craig IR , Bramley PN . Platelet activation in nocturnal asthma. Thorax 46: 197‐200, 1991.
 144. Mostefai HA , Meziani F , Mastronardi ML , Agouni A , Heymes C , Sargentini C , Asfar P , Martinez MC , Andriantsitohaina R . Circulating microparticles from patients with septic shock exert protective role in vascular function. Am J Respir Crit Care Med 178: 1148‐1155, 2008.
 145. Murugappan S , Shankar H , Kunapuli SP . Platelet receptors for adenine nucleotides and thromboxane A2. Semin Thromb Hemost 30: 411‐418, 2004.
 146. Nagalla S , Shaw C , Kong X , Kondkar AA , Edelstein LC , Ma L , Chen J , McKnight GS , López JA , Yang L , Jin Y , Bray MS , Leal SM , Dong J‐F , Bray PF . Platelet microRNA‐mRNA coexpression profiles correlate with platelet reactivity. Blood 117: 5189‐5197, 2011.
 147. Nguyen T , Ghebrehiwet B , Peerschke EI . Staphylococcus aureus protein A recognizes platelet gC1qR/p33: A novel mechanism for staphylococcal interactions with platelets. Infect Immun 68: 2061‐2068, 2000.
 148. Nieuwland R , Berckmans RJ , McGregor S , Böing AN , Romijn FP , Westendorp RG , Hack CE , Sturk A . Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 95: 930‐935, 2000.
 149. Nieuwland R , Berckmans RJ , Rotteveel‐Eijkman RC , Maquelin KN , Roozendaal KJ , Jansen PG , Have ten K , Eijsman L , Hack CE , Sturk A . Cell‐derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 96: 3534‐3541, 1997.
 150. Niiya K , Hodson E , Bader R , Byers‐Ward V , Koziol JA , Plow EF , Ruggeri ZM . Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of fibrinogen and platelet aggregation. Blood 70: 475‐483, 1987.
 151. Owens AP , Mackman N . Microparticles in hemostasis and thrombosis. Circ Res 108: 1284‐1297, 2011.
 152. Pabla R , Weyrich AS , Dixon DA , Bray PF , McIntyre TM , Prescott SM , Zimmerman GA . Integrin‐dependent control of translation: Engagement of integrin alphaIIbbeta3 regulates synthesis of proteins in activated human platelets. J Cell Biol 144: 175‐184, 1999.
 153. Pan Y , Liang H , Liu H , Li D , Chen X , Li L , Zhang C‐Y , Zen K . Platelet‐secreted microRNA‐223 promotes endothelial cell apoptosis induced by advanced glycation end products via targeting the insulin‐like growth factor 1 receptor. J Immunol 192: 437‐446, 2014.
 154. Panigrahi S , Ma Y , Hong L , Gao D , West XZ , Salomon RG , Byzova TV , Podrez EA . Engagement of platelet toll‐like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis. Circ Res 112: 103‐112, 2013.
 155. Papayannopoulos V , Metzler KD , Hakkim A , Zychlinsky A . Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol 191: 677‐691, 2010.
 156. Peerschke EI , Reid KB , Ghebrehiwet B . Identification of a novel 33‐kDa C1q‐binding site on human blood platelets. J Immunol 152: 5896‐5901, 1994.
 157. Peerschke EI , Yin W , Ghebrehiwet B . Complement activation on platelets: Implications for vascular inflammation and thrombosis. Mol Immunol 47: 2170‐2175, 2010.
 158. Peerschke EIB , Yin W , Grigg SE , Ghebrehiwet B . Blood platelets activate the classical pathway of human complement. J Thromb Haemost 4: 2035‐2042, 2006.
 159. Petersen F , Bock L , Flad HD , Brandt E . A chondroitin sulfate proteoglycan on human neutrophils specifically binds platelet factor 4 and is involved in cell activation. J Immunol 161: 4347‐4355, 1998.
 160. Petersen F , Ludwig A , Flad HD , Brandt E . TNF‐alpha renders human neutrophils responsive to platelet factor 4. Comparison of PF‐4 and IL‐8 reveals different activity profiles of the two chemokines. J Immunol 156: 1954‐1962, 1996.
 161. Pilsczek FH , Salina D , Poon KKH , Fahey C , Yipp BG , Sibley CD , Robbins SM , Green FHY , Surette MG , Sugai M , Bowden MG , Hussain M , Zhang K , Kubes P . A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 185: 7413‐7425, 2010.
 162. Piotrowicz RS , Orchekowski RP , Nugent DJ , Yamada KY , Kunicki TJ . Glycoprotein Ic‐IIa functions as an activation‐independent fibronectin receptor on human platelets. J Cell Biol 106: 1359‐1364, 1988.
 163. Pitchford SC , Riffo‐Vasquez Y , Sousa A , Momi S , Gresele P , Spina D , Page CP . Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation. Blood 103: 639‐647, 2004.
 164. Pitchford SC , Yano H , Lever R , Riffo‐Vasquez Y , Ciferri S , Rose MJ , Giannini S , Momi S , Spina D , O'connor B , Gresele P , Page CP . Platelets are essential for leukocyte recruitment in allergic inflammation. J Allergy Clin Immunol 112: 109‐118, 2003.
 165. Power CA , Furness RB , Brawand C , Wells TN . Cloning of a full‐length cDNA encoding the neutrophil‐activating peptide ENA‐78 from human platelets. Gene 151: 333‐334, 1994.
 166. Pytela R , Pierschbacher MD , Ruoslahti E . A 125/115‐kDa cell surface receptor specific for vitronectin interacts with the arginine‐glycine‐aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A 82: 5766‐5770, 1985.
 167. Qian K , Xie F , Gibson AW , Edberg JC , Kimberly RP , Wu J . Functional expression of IgA receptor FcalphaRI on human platelets. J Leukoc Biol 84: 1492‐1500, 2008.
 168. Rahman M , Roller J , Zhang S , Syk I , Menger MD , Jeppsson B , Thorlacius H . Metalloproteinases regulate CD40L shedding from platelets and pulmonary recruitment of neutrophils in abdominal sepsis. Inflamm Res 61: 571‐579, 2012.
 169. Rendu F , Brohard‐Bohn B . The platelet release reaction: Granules' constituents, secretion and functions. Platelets 12: 261‐273, 2001.
 170. Romo GM , Dong JF , Schade AJ , Gardiner EE , Kansas GS , Li CQ , McIntire LV , Berndt MC , López JA . The glycoprotein Ib‐IX‐V complex is a platelet counterreceptor for P‐selectin. J Exp Med 190: 803‐814, 1999.
 171. Rosenfeld SI , Looney RJ , Leddy JP , Phipps DC , Abraham GN , Anderson CL . Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000‐molecular‐weight membrane protein shared by monocytes. J Clin Invest 76: 2317‐2322, 1985.
 172. Ross R . Atherosclerosis‐an inflammatory disease. N Engl J Med 340: 115‐126, 1999.
 173. Rouhiainen A , Imai S , Rauvala H , Parkkinen J . Occurrence of amphoterin (HMG1) as an endogenous protein of human platelets that is exported to the cell surface upon platelet activation. Thromb Haemost 84: 1087‐1094, 2000.
 174. Rubenfeld GD , Herridge MS . Epidemiology and outcomes of acute lung injury. Chest 131: 554‐562, 2007.
 175. Rumbaut RE , Thiagarajan P . Platelet‐Vessel Wall Interactions in Hemostasis and Thrombosis. San Rafael (CA): Morgan & Claypool Life Sciences, 2010.
 176. Sayed D , Abdellatif M . MicroRNAs in development and disease. Physiol Rev 91: 827‐887, 2011.
 177. Scheuerer B , Ernst M , Dürrbaum‐Landmann I , Fleischer J , Grage‐Griebenow E , Brandt E , Flad HD , Petersen F . The CXC‐chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood 95: 1158‐1166, 2000.
 178. Schober A , Manka D , Hundelshausen von P , Huo Y , Hanrath P , Sarembock IJ , Ley K , Weber C . Deposition of platelet RANTES triggering monocyte recruitment requires P‐selectin and is involved in neointima formation after arterial injury. Circulation 106: 1523‐1529, 2002.
 179. Schwertz H , Tolley ND , Foulks JM , Denis MM , Risenmay BW , Buerke M , Tilley RE , Rondina MT , Harris EM , Kraiss LW , Mackman N , Zimmerman GA , Weyrich AS . Signal‐dependent splicing of tissue factor pre‐mRNA modulates the thrombogenicity of human platelets. J Exp Med 203: 2433‐2440, 2006.
 180. Sehgal S , Storrie B . Evidence that differential packaging of the major platelet granule proteins von Willebrand factor and fibrinogen can support their differential release. J Thromb Haemost 5: 2009‐2016, 2007.
 181. Semeraro F , Ammollo CT , Morrissey JH , Dale GL , Friese P , Esmon NL , Esmon CT . Extracellular histones promote thrombin generation through platelet‐dependent mechanisms: Involvement of platelet TLR2 and 4. Blood (June 14, 2011). doi: 10.1182/blood‐2011‐03‐343061.
 182. Semple JW , Italiano JE , Freedman J . Platelets and the immune continuum. Nat Rev Immunol 11: 264‐274, 2011.
 183. Silverstein RL , Febbraio M . Identification of lysosome‐associated membrane protein‐2 as an activation‐dependent platelet surface glycoprotein. Blood 80: 1470‐1475, 1992.
 184. Simon DI , Chen Z , Xu H , Li CQ , Dong JF , McIntire LV , Ballantyne CM , Zhang L , Furman MI , Berndt MC , López JA . Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac‐1 (CD11b/CD18). J Exp Med 192: 193‐204, 2000.
 185. Sims PJ , Wiedmer T , Esmon CT , Weiss HJ , Shattil SJ . Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: An isolated defect in platelet procoagulant activity. J Biol Chem 264: 17049‐17057, 1989.
 186. Sixma JJ , van den Berg A , Hasilik A , Figura von K , Geuze HJ . Immuno‐electron microscopical demonstration of lysosomes in human blood platelets and megakaryocytes using anti‐cathepsin D. Blood 65: 1287‐1291, 1985.
 187. Slichter SJ . Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 18: 153‐167, 2004.
 188. Smith CW , Rothlein R , Hughes BJ , Mariscalco MM , Rudloff HE , Schmalstieg FC , Anderson DC . Recognition of an endothelial determinant for CD 18‐dependent human neutrophil adherence and transendothelial migration. J Clin Invest 82: 1746‐1756, 1988.
 189. Sonnenberg A , Modderman PW , Hogervorst F . Laminin receptor on platelets is the integrin VLA‐6. Nature 336: 487‐489, 1988.
 190. Soriano AO , Jy W , Chirinos JA , Valdivia MA , Velasquez HS , Jimenez JJ , Horstman LL , Kett DH , Schein RMH , Ahn YS . Levels of endothelial and platelet microparticles and their interactions with leukocytes negatively correlate with organ dysfunction and predict mortality in severe sepsis. Crit Care Med 33: 2540‐2546, 2005.
 191. Sreeramkumar V , Adrover JM , Ballesteros I , Cuartero MI , Rossaint J , Bilbao I , Nácher M , Pitaval C , Radovanovic I , Fukui Y , McEver RP , Filippi M‐D , Lizasoain I , Ruiz‐Cabello J , Zarbock A , Moro MA , Hidalgo A . Neutrophils scan for activated platelets to initiate inflammation. Science 346: 1234‐1238, 2014.
 192. Staatz WD , Rajpara SM , Wayner EA , Carter WG , Santoro SA . The membrane glycoprotein Ia‐IIa (VLA‐2) complex mediates the Mg++‐dependent adhesion of platelets to collagen. J Cell Biol 108: 1917‐1924, 1989.
 193. Stark RJ , Aghakasiri N , Rumbaut RE . Platelet‐derived Toll‐like receptor 4 (Tlr‐4) is sufficient to promote microvascular thrombosis in endotoxemia. PLoS ONE 7: e41254, 2012.
 194. Stokes KY , Granger DN . Platelets: A critical link between inflammation and microvascular dysfunction. J Physiol (Lond) 590: 1023‐1034, 2012.
 195. Stratz C , Nührenberg TG , Binder H , Valina CM , Trenk D , Hochholzer W , Neumann FJ , Fiebich BL . Micro‐array profiling exhibits remarkable intra‐individual stability of human platelet micro‐RNA. Thromb Haemost 107: 634‐641, 2012.
 196. Sukhithasri V , Nisha N , Biswas L , Anil Kumar V , Biswas R . Innate immune recognition of microbial cell wall components and microbial strategies to evade such recognitions. Microbiol Res 168: 396‐406, 2013.
 197. Suzuki‐Inoue K , Fuller GLJ , García A , Eble JA , Pöhlmann S , Inoue O , Gartner TK , Hughan SC , Pearce AC , Laing GD , Theakston RDG , Schweighoffer E , Zitzmann N , Morita T , Tybulewicz VLJ , Ozaki Y , Watson SP . A novel Syk‐dependent mechanism of platelet activation by the C‐type lectin receptor CLEC‐2. Blood 107: 542‐549, 2006.
 198. Svensson L , Baumgarten M , Mörgelin M , Shannon O . Platelet activation by Streptococcus pyogenes leads to entrapment in platelet aggregates, from which bacteria subsequently escape. Infect Immun 82: 4307‐4314, 2014.
 199. Terao S , Yilmaz G , Stokes KY , Russell J , Ishikawa M , Kawase T , Granger DN . Blood cell‐derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia‐reperfusion. Stroke 39: 2560‐2570, 2008.
 200. Tutluoglu B , Gurel CB , Ozdas SB , Musellim B , Erturan S , Anakkaya AN , Kilinc G , Ulutin T . Platelet function and fibrinolytic activity in patients with bronchial asthma. Clin Appl Thromb Hemost 11: 77‐81, 2005.
 201. Urban CF , Reichard U , Brinkmann V , Zychlinsky A . Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 8: 668‐676, 2006.
 202.Van Aken WG , Vreeken J . Accumulaon of macromolecular particles in the reticuloendothelial system (RES) mediated by platelet aggregation and disaggregation. Thromb Diath Haemorrh 22: 496‐507, 1969.
 203.Van Raemdonck K , Gouwy M , Lepers SA , Van Damme J , Struyf S . CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular endothelial cells and activated lymphocytes: Involvement of mitogen‐activated protein (MAP) kinases, Src and p70S6 kinase. Angiogenesis 17: 631‐640, 2014.
 204. Vanichakarn P , Blair P , Wu C , Freedman JE , Chakrabarti S . Neutrophil CD40 enhances platelet‐mediated inflammation. Thromb Res 122: 346‐358, 2008.
 205. Voudoukis E . Multipotent role of platelets in inflammatory bowel diseases: A clinical approach. WJG 20: 3180, 2014.
 206. Vowinkel T , Anthoni C , Wood KC , Stokes KY , Russell J , Gray L , Bharwani S , Senninger N , Alexander JS , Krieglstein CF , Grisham MB , Granger DN . CD40‐CD40 ligand mediates the recruitment of leukocytes and platelets in the inflamed murine colon. Gastroenterology 132: 955‐965, 2007.
 207. Wagner CL , Mascelli MA , Neblock DS , Weisman HF , Coller BS , Jordan RE . Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 88: 907‐914, 1996.
 208. Wagner DD , Frenette PS . The vessel wall and its interactions. Blood 111: 5271‐5281, 2008.
 209. Wang H‐B , Wang J‐T , Zhang L , Geng ZH , Xu W‐L , Xu T , Huo Y , Zhu X , Plow EF , Chen M , Geng J‐G . P‐selectin primes leukocyte integrin activation during inflammation. Nat Immunol 8: 882‐892, 2007.
 210. Wang Y , Sakuma M , Chen Z , Ustinov V , Shi C , Croce K , Zago AC , Lopez J , Andre P , Plow E , Simon DI . Leukocyte engagement of platelet glycoprotein Ibalpha via the integrin Mac‐1 is critical for the biological response to vascular injury. Circulation 112: 2993‐3000, 2005.
 211. Warshaw AL , Laster L , Shulman NR . Protein synthesis by human platelets. J Biol Chem 242: 2094‐2097, 1967.
 212. Weber C , Springer TA . Neutrophil accumulation on activated, surface‐adherent platelets in flow is mediated by interaction of Mac‐1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet‐activating factor. J Clin Invest 100: 2085‐2093, 1997.
 213. Weissmann G . The role of lysosomes in inflammation and disease. Annu Rev Med 18: 97‐112, 1967.
 214. Weyrich AS , Dixon DA , Pabla R , Elstad MR , McIntyre TM , Prescott SM , Zimmerman GA . Signal‐dependent translation of a regulatory protein, Bcl‐3, in activated human platelets. Proc Natl Acad Sci U S A 95: 5556‐5561, 1998.
 215. Weyrich AS , Elstad MR , McEver RP , McIntyre TM , Moore KL , Morrissey JH , Prescott SM , Zimmerman GA . Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 97: 1525‐1534, 1996.
 216. Weyrich AS , McIntyre TM , McEver RP , Prescott SM , Zimmerman GA . Monocyte tethering by P‐selectin regulates monocyte chemotactic protein‐1 and tumor necrosis factor‐alpha secretion. Signal integration and NF‐kappa B translocation. J Clin Invest 95: 2297‐2303, 1995.
 217. Weyrich AS , Schwertz H , Kraiss LW , Zimmerman GA . Protein synthesis by platelets: Historical and new perspectives. J Thromb Haemost 7: 241‐246, 2009.
 218. White JG . Why human platelets fail to kill bacteria. Platelets 17: 191‐200, 2006.
 219. White JG . Platelet structure. In: Michelson AD , editor. Platelets. Academic Press, 2007, pp. 45‐73.
 220. White JG , Clawson CC . The surface‐connected canalicular system of blood platelets‐a fenestrated membrane system. Am J Pathol 101: 353‐364, 1980.
 221. White JG , Krumwiede MD , Escolar G . Glycoprotein Ib is homogeneously distributed on external and internal membranes of resting platelets. Am J Pathol 155: 2127‐2134, 1999.
 222. Xie J , Li R , Kotovuori P , Vermot‐Desroches C , Wijdenes J , Arnaout MA , Nortamo P , Gahmberg CG . Intercellular adhesion molecule‐2 (CD102) binds to the leukocyte integrin CD11b/CD18 through the A domain. J Immunol 155: 3619‐3628, 1995.
 223. Xu J , Zhang X , Monestier M , Esmon NL , Esmon CT . Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. J Immunol 187: 2626‐2631, 2011.
 224. Xu T , Zhang L , Geng ZH , Wang H‐B , Wang J‐T , Chen M , Geng J‐G . P‐selectin cross‐links PSGL‐1 and enhances neutrophil adhesion to fibrinogen and ICAM‐1 in a Src kinase‐dependent, but GPCR‐independent mechanism. Cell Adh Migr 1: 115‐123, 2007.
 225. Yeaman MR , Bayer AS , Koo SP , Foss W , Sullam PM . Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. J Clin Invest 101: 178‐187, 1998.
 226. Yeaman MR , Ibrahim AS , Edwards JE , Bayer AS , Ghannoum MA . Thrombin‐induced rabbit platelet microbicidal protein is fungicidal in vitro. Antimicrob Agents Chemother 37: 546‐553, 1993.
 227. Yeaman MR , Puentes SM , Norman DC , Bayer AS . Partial characterization and staphylocidal activity of thrombin‐induced platelet microbicidal protein. Infect Immun 60: 1202‐1209, 1992.
 228. Yeaman MR , Soldan SS , Ghannoum MA , Edwards JE , Filler SG , Bayer AS . Resistance to platelet microbicidal protein results in increased severity of experimental Candida albicans endocarditis. Infect Immun 64: 1379‐1384, 1996.
 229. Youssefian T , Drouin A , Massé J‐M , Guichard J , Cramer EM . Host defense role of platelets: Engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 99: 4021‐4029, 2002.
 230. Zarbock A , Polanowska‐Grabowska RK , Ley K . Platelet‐neutrophil‐interactions: Linking hemostasis and inflammation. Blood Rev 21: 99‐111, 2007.
 231. Zarbock A , Singbartl K , Ley K . Complete reversal of acid‐induced acute lung injury by blocking of platelet‐neutrophil aggregation. J Clin Invest 116: 3211‐3219, 2006.
 232. Zhang X , Zhan D , Shin HY . Integrin subtype‐dependent CD18 cleavage under shear and its influence on leukocyte‐platelet binding. J Leukoc Biol 93: 251‐258, 2013.
 233. Zucker‐Franklin D , Seremetis S , Zheng ZY . Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets. Blood 75: 1920‐1923, 1990.
 234. Zufferey A , Schvartz D , Nolli S , Reny J‐L , Sanchez J‐C , Fontana P . Characterization of the platelet granule proteome: Evidence of the presence of MHC1 in alpha‐granules. J Proteomics 101: 130‐140, 2014.

Related Articles:

Platelet‐Blood Vessel Interactions
The Microcirculation in Inflammation
Immune System
Fever, Immunity, and Molecular Adaptations
Cellular Immunology
Immunity and Inflammation

Contact Editor

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

* Required Field

Article Title: Platelets and Their Interactions with Other Immune Cells
 

How to Cite

Fong W. Lam, K. Vinod Vijayan, Rolando E. Rumbaut. Platelets and Their Interactions with Other Immune Cells . Compr Physiol 2015, 5: 1265-1280. doi: 10.1002/cphy.c140074