Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.

作者: P R Galle , W J Hofmann , H Walczak , H Schaller , G Otto

DOI: 10.1084/JEM.182.5.1223

关键词:

摘要: Apoptosis occurs in the normal liver and various forms of disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, cells animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system investigate CD95-mediated apoptotic damage. Treatment fresh with low concentrations agonistic antibodies against resulted > 95% cultured within 4 7.5 h. Immunohistology panel explanted tissues revealed that livers (n = 5) alcoholic cirrhosis 13) expressed constitutive levels CD95. expression was highly elevated hepatitis B virus-related 9) acute failure 8). By situ hybridization ligand messenger RNA absent but detected at high ongoing In cases hepatic failure, found primarily areas lymphocytic infiltration. contrast, patients damage, hepatocytes. These findings suggest destruction may involve killing T lymphocytes using receptor-ligand system. death might occur fratricide paracrine or autocrine mechanisms mediated themselves.

参考文章(47)
K. M. Debatin, C. Henne, K. Koretz, P. H. Krammer, G. Mechtersheimer, A. Schmidt, S. Bruderlein, F. Leithauser, J. Dhein, P. Moller, Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Laboratory Investigation. ,vol. 69, pp. 415- 429 ,(1993)
T Stalder, P Erb, S Hahn, Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity. Journal of Immunology. ,vol. 152, pp. 1127- 1133 ,(1994)
A Oehm, I Behrmann, W Falk, M Pawlita, G Maier, C Klas, M Li-Weber, S Richards, J Dhein, B.C. Trauth, Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. Journal of Biological Chemistry. ,vol. 267, pp. 10709- 10715 ,(1992) , 10.1016/S0021-9258(19)50076-X
Bernhard C. Trauth, Jens Dhein, Peter T. Daniel, Peter H. Krammer, Alex Oehm, Peter Möller, Induction of apoptosis by monoclonal antibody anti-APO-1 class switch variants is dependent on cross-linking of APO-1 cell surface antigens. Journal of Immunology. ,vol. 149, pp. 3166- 3173 ,(1992)
Peter R. Galle, Jens Hagelstein, Burkhard Kommerell, Martin Volkmann, Peter Schranz, Hanswalter Zentgraf, In vitro experimental infection of primary human hepatocytes with hepatitis B virus. Gastroenterology. ,vol. 106, pp. 664- 673 ,(1994) , 10.1016/0016-5085(94)90700-5
F V Chisari, R Nayersina, S Guilhot, G Missale, P Fowler, A G Redeker, R Chesnut, A Cerny, H J Schlicht, J L Person, A Vitiello, HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. Journal of Immunology. ,vol. 150, pp. 4659- 4671 ,(1993)
T Suda, S Nagata, Purification and characterization of the fas-ligand that induces apoptosis Journal of Experimental Medicine. ,vol. 179, pp. 873- 879 ,(1994) , 10.1084/JEM.179.3.873
D. J. Pickup, B. S. Ink, W. Hu, C. A. Ray, W. K. Joklik, Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases Proceedings of the National Academy of Sciences of the United States of America. ,vol. 83, pp. 7698- 7702 ,(1986) , 10.1073/PNAS.83.20.7698
Peter R. Galle, Lorenz Theilmann, Richard Raedsch, Gerd Otto, Adolf Stiehl, Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes Hepatology. ,vol. 12, pp. 486- 491 ,(1990) , 10.1002/HEP.1840120307
S. T. Ju, H. Cui, D. J. Panka, R. Ettinger, A. Marshak-Rothstein, Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 4185- 4189 ,(1994) , 10.1073/PNAS.91.10.4185