Macrophage-mediated phagocytosis of apoptotic cholangiocytes contributes to reversal of experimental biliary fibrosis

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 298, Issue 3, 2010, Pages

  Popov, Yury ^a,b   Sverdlov, Deanna Y ^a   Bhaskar, K Ramakrishnan ^a   Sharma, Anisha K ^a   Millonig, Gunda ^a   Patsenker, Eleonora ^b,c   Krahenbuhl, Stephan ^d   Krahenbuhl, Lukas ^e   Schuppan, Detlef ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c UNIVERSITY OF BERN   (Switzerland)

^d UNIVERSITY HOSPITAL BASEL   (Switzerland)

^e Hopital Cantonal de Fribourg   (Switzerland)

Author keywords

Animal model; Bile duct; Cirrhosis; Collagen; Collagenase; Extracellular matrix; Gelatinase; Hepatic stellate cell; Integrin v 6; Kupffer cell; Liver fibrosis resolution; Matrix metalloproteinase; PDGF; Phagocyte; Repair; Tissue inhibitor of matrix metalloproteinases; Transforming growth factor ; Urokinase plasminogen activator receptor 1; Zymography

Indexed keywords

CHLORDANE; COLLAGEN; CYTOKERATIN 19; GELATINASE B; MESSENGER RNA; NEUTROPHIL COLLAGENASE; STROMELYSIN;

ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BILE DUCT; BILE DUCT LIGATION; BILIARY FIBROSIS; BILIARY TRACT DISEASE; CHOLANGIOCYTE; CONTROLLED STUDY; ENZYME ACTIVITY; EPITHELIUM CELL; GENE EXPRESSION; HISTOLOGY; IN VITRO STUDY; LIVER; MALE; NONHUMAN; PERITONEUM MACROPHAGE; PHAGOCYTOSIS; PRIORITY JOURNAL; RAT; ROUX Y ANASTOMOSIS;

ANASTOMOSIS, ROUX-EN-Y; ANIMALS; APOPTOSIS; BILE DUCTS, EXTRAHEPATIC; BILE DUCTS, INTRAHEPATIC; CELL LINE; CELL MOVEMENT; CELLS, CULTURED; COLLAGEN; COLLAGEN TYPE I; COLLAGENASES; DOWN-REGULATION; GELATINASES; GENE EXPRESSION; INTEGRIN BETA CHAINS; LIGATION; LIVER; LIVER CIRRHOSIS, BILIARY; LIVER CIRRHOSIS, EXPERIMENTAL; MACROPHAGES; MALE; MATRIX METALLOPROTEINASES; MICE; MODELS, BIOLOGICAL; PHAGOCYTOSIS; PLASMINOGEN ACTIVATOR INHIBITOR 1; RATS; RATS, SPRAGUE-DAWLEY; TISSUE INHIBITOR OF METALLOPROTEINASE-1; TRANSFORMING GROWTH FACTOR BETA;

EID: 77249139206     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00394.2009     Document Type: Article

References (47)

1. Abdel-Aziz G, Lebeau G, Rescan PY, Clement B, Rissel M, Deugnier Y, Campion JP, Guillouzo A. Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. Am J Pathol 137: 1333-1342, 1990.
2. Aronson DC, Chamuleau RA, Frederiks WM, Gooszen HG, Heijmans HS, James J. Reversibility of cholestatic changes following experimental common bile duct obstruction: fact or fantasy? J Hepatol 18: 85-95, 1993.
3. Canbay A, Feldstein A, Baskin-Bey E, Bronk SF, Gores GJ. The caspase inhibitor IDN-6556 attenuates hepatic injury and fibrosis in the bile duct ligated mouse. J Pharmacol Exp Ther 308: 1191-1196, 2004.
4. Canbay A, Feldstein AE, Higuchi H, Werneburg N, Grambihler A, Bronk SF, Gores GJ. Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression. Hepatology 38: 1188-1198, 2003.
5. Canbay A, Higuchi H, Bronk SF, Taniai M, Sebo TJ, Gores GJ. Fas enhances fibrogenesis in the bile duct ligated mouse: a link between apoptosis and fibrosis. Gastroenterology 123: 1323-1330, 2002.
6. Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 83: 655-663, 2003.
7. Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. Hepatology 41: 809-818, 2005.
8. Costa AM, Tuchweber B, Lamireau T, Yousef IM, Balabaud C, Rosenbaum J, Desmouliere A. Role of apoptosis in the remodeling of cholestatic liver injury following release of the mechanical stress. Virchows Arch 442: 372-380, 2003.
9. Dan Z, Popov Y, Patsenker E, Preimel D, Liu C, Wang XD, Seitz HK, Schuppan D, Stickel F. Hepatotoxicity of alcohol-induced polar retinol metabolites involves apoptosis via loss of mitochondrial membrane potential. FASEB J 19: 845-847, 2005.
10. Davies SE, Portmann BC, O'Grady JG, Aldis PM, Chaggar K, Alexander GJ, Williams R. Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis. Hepatology 13: 150-157, 1991.
11. Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol 40: 860-867, 2004.
12. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, Wu S, Lang R, Iredale JP. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 115: 56-65, 2005.
13. Edwards JP, Zhang X, Frauwirth KA, Mosser DM. Biochemical and functional characterization of three activated macrophage populations. J Leukoc Biol 80: 1298-1307, 2006.
14. Fallowfield JA, Mizuno M, Kendall TJ, Constandinou CM, Benyon RC, Duffield JS, Iredale JP. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J Immunol 178: 5288-5295, 2007.
15. Fickert P, Trauner M, Fuchsbichler A, Zollner G, Wagner M, Marschall HU, Zatloukal K, Denk H. Oncosis represents the main type of cell death in mouse models of cholestasis. J Hepatol 42: 378-385, 2005.
16. Friedman SL. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nat Clin Pract Gastroenterol Hepatol 1: 98-105, 2004.
17. Friedman SL, Bansal MB. Reversal of hepatic fibrosis-fact or fantasy? Hepatology 43: S82-S88, 2006.
18. Greenwel P, Schwartz M, Rosas M, Peyrol S, Grimaud JA, Rojkind M. Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6. Lab Invest 65: 644-653, 1991.
19. Hanada S, Harada M, Koga H, Kawaguchi T, Taniguchi E, Kumashiro R, Ueno T, Ueno Y, Ishii M, Sakisaka S, Sata M. Tumor necrosis factor-alpha and interferon-gamma directly impair epithelial barrier function in cultured mouse cholangiocytes. Liver Int 23: 3-11, 2003.
20. Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 6: 480-498, 2007.
21. Iredale JP. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 117: 539-548, 2007.
22. Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 102: 538-549, 1998.
23. Issa R, Williams E, Trim N, Kendall T, Arthur MJ, Reichen J, Benyon RC, Iredale JP. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut 48: 548-557, 2001.
24. Issa R, Zhou X, Constandinou CM, Fallowfield J, Millward-Sadler H, Gaca MD, Sands E, Suliman I, Trim N, Knorr A, Arthur MJ, Benyon RC, Iredale JP. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 126: 1795-1808, 2004.
25. Krysko DV, D'Herde K, Vandenabeele P. Clearance of apoptotic and necrotic cells and its immunological consequences. Apoptosis 11: 1709-1726, 2006.
26. Krysko DV, Vandenabeele P. From regulation of dying cell engulfment to development of anti-cancer therapy. Cell Death Differ 15: 29-38, 2008.
27. Lang C, Berardi S, Schafer M, Serra D, Hegardt FG, Krahenbuhl L, Krahenbuhl S. Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction. J Hepatol 37: 564-571, 2002.
28. McCawley LJ, Matrisian LM. Matrix metalloproteinases: they're not just for matrix anymore!. Curr Opin Cell Biol 13: 534-540, 2001.
29. Milani S, Herbst H, Schuppan D, Kim KY, Riecken EO, Stein H. Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis. Gastroenterology 98: 175-184, 1990.
30. Milani S, Herbst H, Schuppan D, Stein H, Surrenti C. Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease. Am J Pathol 139: 1221-1229, 1991.
31. Olaso E, Ikeda K, Eng FJ, Xu L, Wang LH, Lin HC, Friedman SL. DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest 108: 1369-1378, 2001.
32. Omenetti A, Popov Y, Jung Y, Choi SS, Witek RP, Yang L, Brown KD, Schuppan D, Diehl AM. The hedgehog pathway regulates remodelling responses to biliary obstruction in rats. Gut 57: 1275-1282, 2008.
33. Patsenker E, Popov Y, Stickel F, Jonczyk A, Goodman SL, Schuppan D. Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression. Gastroenterology 135: 660-670, 2008.
34. Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, Caligiuri A, Pellegrini G, Ngo DV, Romanelli RG, Gentilini P. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol 148: 785-800, 1996.
35. Popov Y, Patsenker E, Bauer M, Niedobitek E, Schulze-Krebs A, Schuppan D. Halofuginone induces matrix metalloproteinases in rat hepatic stellate cells via activation of p38 and NFkappaB. J Biol Chem 281: 15090-15098, 2006.
36. Popov Y, Patsenker E, Fickert P, Trauner M, Schuppan D. Mdr2 (Abcb4)-/- mice spontaneously develop severe biliary fibrosis via massive dysregulation of pro- and antifibrogenic genes. J Hepatol 43: 1045-1054, 2005.
37. Popov Y, Patsenker E, Stickel F, Zaks J, Bhaskar KR, Niedobitek G, Kolb A, Friess H, Schuppan D. Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies. J Hepatol 48: 453-464, 2008.
38. Ra HJ, Parks WC. Control of matrix metalloproteinase catalytic activity. Matrix Biol 26: 587-596, 2007.
39. Ray MB, Mendenhall CL, French SW, Gartside PS. Bile duct changes in alcoholic liver disease. The Veterans Administration Cooperative Study Group. Liver 13: 36-45, 1993.
40. Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, Dixon JB, Weltman MD, Tilg H, Moschen AR, Purdie DM, Demetris AJ, Clouston AD. Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology 133: 80-90, 2007.
41. Rosenblum G, Van den Steen PE, Cohen SR, Grossmann JG, Frenkel J, Sertchook R, Slack N, Strange RW, Opdenakker G, Sagi I. Insights into the structure and domain flexibility of full-length pro-matrix metalloproteinase-9/ gelatinase B. Structure 15: 1227-1236, 2007.
42. Sather S, Kenyon KD, Lefkowitz JB, Liang X, Varnum BC, Henson PM, Graham DK. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood 109: 1026-1033, 2007.
43. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 371: 838-851, 2008.
44. Sedlaczek N, Jia JD, Bauer M, Herbst H, Ruehl M, Hahn EG, Schuppan D. Proliferating bile duct epithelial cells are a major source of connective tissue growth factor in rat biliary fibrosis. Am J Pathol 158: 1239-1244, 2001.
45. Shipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci USA 93: 3942-3946, 1996.
46. Wang B, Dolinski BM, Kikuchi N, Leone DR, Peters MG, Weinreb PH, Violette SM, Bissell DM. Role of alphavbeta6 integrin in acute biliary fibrosis. Hepatology 46: 1404-1412, 2007.
47. Winwood PJ, Schuppan D, Iredale JP, Kawser CA, Docherty AJ, Arthur MJ. Kupffer cell-derived 95-kd type IV collagenase/gelatinase B: characterization and expression in cultured cells. Hepatology 22: 304-315, 1995.