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Pathways and Functions of Biliary Protein Secretion

Albert L. Jones, Susan Jo Burwen

10.1002/cphy.cp060332

Source: Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Anatomy of Biliary Protein Secretion
1.1 Liver
1.2 Hepatocyte
2 Receptor‐Mediated Endocytosis and Intracellular Transport Pathways
2.1 Lysosomal Degradation (Degradative Pathway)
2.2 Secretion of Intact Proteins into Bile (Transcellular Pathway)
2.3 Utilization by Hepatocytes
2.4 Mechanisms of Pathway Regulation
3 Role of The Cytoskeleton in Protein Transport by Hepatocytes
4 Functional Significance of Hepatobiliary Protein Secretion
4.1 Intestinal Immune Response
4.2 Biliary Cholesterol Metabolism
4.3 Pathophysiological Conditions
4.4 Functional Significance of Hepatobiliary Transport of Epidermal Growth Factor
Figure 1. Figure 1.

Electron micrograph of normal rat hepatocyte. Microvillus (MV) is protruding through endothelial cell fenestrae (F) directly into the sinusoid (S). Numerous clathrin‐coated pits and vesicles (arrowheads) are visible adjacent to sinusoidal plasma membrane. CT, connective tissue. Bar, 1 μm.
Figure 2. Figure 2.

Diagrammatic representation of structure of liver lobule. BD, bile duct; PV, portal vein; HA, hepatic artery; TPV, terminal portal venule; CV, central vein.

From Jones and Schmucker 38
Figure 3. Figure 3.

Immunofluorescent staining of microtubules in rat hepatocytes in primary monolayer culture. Microtubules radiate from multiple microtubule organizing centers in perinuclear regions of cells. Bar, 10 μm.

Light micrograph courtesy of J. M. Caron.
Figure 4. Figure 4.

Peribiliary plexus as visualized by methacrylate injection replica scanning electron microscopy. Plexus consists of an inner capillary network and an outer venous network. Bar, 200 μm.

From Ohtani 54
Figure 5. Figure 5.

Diagram depicts 7 major steps in macromolecular processing in degradative or lysosomal pathway. Although only lipoprotein remnants and low‐density lipoproteins (LDL) are shown, steps are identical for all ligands entering this pathway. Taillike appendage that appears to be leaving the multivesicular body (MVB) in step 5 may contain receptors that are in the process of recycling. Primary lysosomes derived from the Golgi, endoplasmic reticulum, lysosome (GERL) region of the cell fuse with MVB and release their acid‐activated hydrolases into acidic interior of MVB. This results in degradation of MVB contents accompanied by a gradual condensation of MVB into a dense secondary lysosome or residual body. BC, bile canaliculus.

From Jones and Burwen 32
Figure 6. Figure 6.

Electron‐microscopic autoradiograph showing association of silver grains with endocytic vesicles (arrowheads) in vicinity of bile canaliculi (BC) 30 min after injection of 125I‐labeled IgA into rat portal vein. Bar, 1 μm.

From Renston et al. 57,© 1980 by the American Association for the Advancement of Science
Figure 7. Figure 7.

Schematic diagram representing several possible pathways whereby IgA entering hepatocytes or biliary space may be regurgitated back into plasma. Evidence supports utilization of a direct transport pathway across parenchymal (3) cells. There is no experimental evidence for the paracellular route through tight junctional complexes (2 and 5). n, Nucleus; G, Golgi; L, lysosomes.

From Jones et al. 36,© 1984 by the American Association for the Study of Liver Diseases.
Figure 8. Figure 8.

Anti‐EGF immunoprecipitable radioactivity secreted into bile, expressed as a percentage of total. 125I‐labeled EGF was injected into rat portal veins, and bile was collected via cannulae over 10‐min intervals. Bile was immunoprecipitated with rabbit anti‐mouse EGF antisera. ▴, Rats pretreated with chloroquine [number of rats (n) = 5]; •, rats pretreated with saline (controls; n = 4). Error bars, standard error of mean.

From Burwen et al. 6
Figure 9. Figure 9.

Total and immunoprecipitable radioactivity in rat bile collected over a period of 50 min after intraportal injection of 125I‐labeled EGF. •, Total radioactivity [control; number of rats (n) = 4]; ▴, total radioactivity, chloroquine pretreated (n = 5); ○;, immunoprecipitable radioactivity (control; n = 4); Δ, immunoprecipitable radioactivity, chloroquine pretreated (n = 5). Error bars, standard error of mean.

From Burwen et al. 6
Figure 10. Figure 10.

A: dimeric IgA (dIgA) binds to its receptor, secretory component (SC), monovalently through disulfide linkages. However, IgG anti‐SC antibody binds in a polyvalent fashion that may result in receptor cross‐linking and aggregation. B: SC‐receptor aggregation may result in degradation of both receptor and ligand via lysosomal (indirect) pathway, rather than their direct transport into bile intact. This phenomenon may be a physiological mechanism for selective degradation of circulating dIgA‐antigen complexes. sIgA, secretory IgA.

From Kim et al. 43
Figure 11. Figure 11.

Electron micrograph of bile canalicular region of hepatocyte from rat with extrahepatic cholestasis. Numerous endocytic vesicles (arrowheads) are in close association with microtubules (MT). Bar, 1 μm.

From Renston et al. 59,© 1983 by the American Association for the Study of Liver Diseases


Figure 1.

Electron micrograph of normal rat hepatocyte. Microvillus (MV) is protruding through endothelial cell fenestrae (F) directly into the sinusoid (S). Numerous clathrin‐coated pits and vesicles (arrowheads) are visible adjacent to sinusoidal plasma membrane. CT, connective tissue. Bar, 1 μm.



Figure 2.

Diagrammatic representation of structure of liver lobule. BD, bile duct; PV, portal vein; HA, hepatic artery; TPV, terminal portal venule; CV, central vein.

From Jones and Schmucker 38


Figure 3.

Immunofluorescent staining of microtubules in rat hepatocytes in primary monolayer culture. Microtubules radiate from multiple microtubule organizing centers in perinuclear regions of cells. Bar, 10 μm.

Light micrograph courtesy of J. M. Caron.


Figure 4.

Peribiliary plexus as visualized by methacrylate injection replica scanning electron microscopy. Plexus consists of an inner capillary network and an outer venous network. Bar, 200 μm.

From Ohtani 54


Figure 5.

Diagram depicts 7 major steps in macromolecular processing in degradative or lysosomal pathway. Although only lipoprotein remnants and low‐density lipoproteins (LDL) are shown, steps are identical for all ligands entering this pathway. Taillike appendage that appears to be leaving the multivesicular body (MVB) in step 5 may contain receptors that are in the process of recycling. Primary lysosomes derived from the Golgi, endoplasmic reticulum, lysosome (GERL) region of the cell fuse with MVB and release their acid‐activated hydrolases into acidic interior of MVB. This results in degradation of MVB contents accompanied by a gradual condensation of MVB into a dense secondary lysosome or residual body. BC, bile canaliculus.

From Jones and Burwen 32


Figure 6.

Electron‐microscopic autoradiograph showing association of silver grains with endocytic vesicles (arrowheads) in vicinity of bile canaliculi (BC) 30 min after injection of 125I‐labeled IgA into rat portal vein. Bar, 1 μm.

From Renston et al. 57,© 1980 by the American Association for the Advancement of Science


Figure 7.

Schematic diagram representing several possible pathways whereby IgA entering hepatocytes or biliary space may be regurgitated back into plasma. Evidence supports utilization of a direct transport pathway across parenchymal (3) cells. There is no experimental evidence for the paracellular route through tight junctional complexes (2 and 5). n, Nucleus; G, Golgi; L, lysosomes.

From Jones et al. 36,© 1984 by the American Association for the Study of Liver Diseases.


Figure 8.

Anti‐EGF immunoprecipitable radioactivity secreted into bile, expressed as a percentage of total. 125I‐labeled EGF was injected into rat portal veins, and bile was collected via cannulae over 10‐min intervals. Bile was immunoprecipitated with rabbit anti‐mouse EGF antisera. ▴, Rats pretreated with chloroquine [number of rats (n) = 5]; •, rats pretreated with saline (controls; n = 4). Error bars, standard error of mean.

From Burwen et al. 6


Figure 9.

Total and immunoprecipitable radioactivity in rat bile collected over a period of 50 min after intraportal injection of 125I‐labeled EGF. •, Total radioactivity [control; number of rats (n) = 4]; ▴, total radioactivity, chloroquine pretreated (n = 5); ○;, immunoprecipitable radioactivity (control; n = 4); Δ, immunoprecipitable radioactivity, chloroquine pretreated (n = 5). Error bars, standard error of mean.

From Burwen et al. 6


Figure 10.

A: dimeric IgA (dIgA) binds to its receptor, secretory component (SC), monovalently through disulfide linkages. However, IgG anti‐SC antibody binds in a polyvalent fashion that may result in receptor cross‐linking and aggregation. B: SC‐receptor aggregation may result in degradation of both receptor and ligand via lysosomal (indirect) pathway, rather than their direct transport into bile intact. This phenomenon may be a physiological mechanism for selective degradation of circulating dIgA‐antigen complexes. sIgA, secretory IgA.

From Kim et al. 43


Figure 11.

Electron micrograph of bile canalicular region of hepatocyte from rat with extrahepatic cholestasis. Numerous endocytic vesicles (arrowheads) are in close association with microtubules (MT). Bar, 1 μm.

From Renston et al. 59,© 1983 by the American Association for the Study of Liver Diseases
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Article Title: Pathways and Functions of Biliary Protein Secretion
 

How to Cite

Albert L. Jones, Susan Jo Burwen. Pathways and Functions of Biliary Protein Secretion. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 663-675. First published in print 1989. doi: 10.1002/cphy.cp060332