Abstract
Cytotoxic T lymphocytes (CTLs) play an important role in the pathogenesis of viral hepatitis. We studied the expression of mRNAs of perforin and Fas ligand (Fas-L) in biopsy specimens from chronic hepatitis B (CHB) (15 cases) and hepatitis C (CHC) patients (13 cases). Both perforin and Fas-L mRNAs were detected in all cases of both CHB and CHC. No messages were detected in the control livers from two cases of fatty liver, a case of Gilbert's syndrome, and a case of Dubin–Johnson syndrome. Semiquantitative analysis revealed a positive correlation between the intensity of perforin and Fas-L mRNAs in both CHB and CHC. In CHB, the intensity of both perforin and Fas-L mRNAs showed a positive correlation with the histological activity and serum alanine aminotransferase level, while the correlation was not apparent in CHC. These results suggest that both perforin and Fas/Fas-L systems are involved in the pathogenesis of liver cell injury of CHB and CHC.
Similar content being viewed by others
REFERENCES
Hoofnagle JH, Alter HJ: Chronic viral hepatitis. In Viral Hepatitis and Liver Disease, GN Vyas, JL Dienstag, JH Hoofnagle, (eds). Orlando, FL, Grune & Stratton, 1984, pp 97-113
Blum HE: Does hepatitis C virus cause hepatocellular carcinoma? Hepatology 19:251-253, 1994
Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RNM, Phillips MJ, Portmann BG, Poulsen H, Scheuer PJ, Schmid M, Thaler H: Histological grading and staging of chronic hepatitis. J Hepatol 22:696-699, 1995
Kerr JFR, Wyllie AH, Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239-257, 1972
Kerr JF, Cooksley WG, Searle J, Halliday JW, Halliday WJ, Holder L, Roberts I, Burnett W, Powell LW: The nature of piecemeal necrosis in chronic active hepatitis. Lancet 2:827-828, 1979
Penna A, Chisari FV, Bertoletti A, Missale G, Fowler P, Giuberti T, Fiaccadori F, Ferrari C: Cytotoxic T lymphocytes recognize an HLA-A2-restricted epitope within the hepatitis B virus nucleocapsid antigen. J Exp Med 174:1565-1570, 1991
Koziel MJ, Dudley D, Wong JT, Dienstag J, Houghton M, Ralston R, Walker BD: Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol 149:3339-3344, 1992
Cerny A, McHutchison JG, Pasquinelli G, Brown ME, Brothers MA, Grabsheid B, Fowler P, Houghton M, Chisari FV: Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing HLA A2.1 binding motif. J Clin Invest 9:521-530, 1995
Weiner A, Erickson AL, Kansopon J, Crawford K, Muchmore E, Hughes AL, Houghton M, Walker CM: Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant. Proc Natl Acad Sci USA 28:2755-2759, 1995
Hur GM, Lee YI, Suh DJ, Lee JH, Lee YI: Gradual accumulation of mutations in precore coreregion of HBV inpatients with chronic active hepatitis: implications of clustering changes in a small region of the HBV core region. J Med Virol 48:38-47, 1996
Kagi D, Vinaux F, Ledermann B, Burki K, Depraetere V, Nagata S, Hengartner H, Golstein P: Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265:528-530, 1994
Liu C-C, Walsh CM, Young D-E: Perforin: Structure and function. Immunol Today 16:194-201, 1995
Watanabe-Fukunaga R, Brannan CI, Itoh N, Yonehara S, Copeland NG, Jenkins NA, Nagata S: The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol 148:1274-1279, 1992
Takahashi T, Tanaka M, Inazawa J, Abe T, Suda T, Nagata S: Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol 6:1567-1574, 1994
Lynch DH, Ramsdell F, Alderson MR: Fas and FasL in the homeostatic regulation of immune responses. Immunol Today 16:569-574, 1995
Ogasawara J, Watanabe-Fukunaga R, Adachi M, Matsuzawa A, Kitamura Y, Itoh N, Suda T, Nagata S: Lethal effects of the anti-Fas antibody in mice. Nature 364:806-809, 1993
Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S: Essential roles of the Fas ligand in the development of hepatitis. Nature Med 3:409-413, 1997
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156-159, 1987
Ohmoto M, Yamamoto K, Nagano T, Matsumoto S, Kobashi H, Okamoto R, Tsuji T: Accumulation of multiple T-cell clonotypes in the liver of primary biliary cirrhosis. Hepatology 25:33-37, 1997
Nagano T, Yamamoto K, Matsumoto S, Okamoto R, Tagashira M, Ibuki N, Matsumura S, Yabushita K, Okano N, Tsuji T: Cytokine expression in liver of primary biliary cirrhosis. J Clin Immunol 19:422-427, 1999
Matsumoto S, Yamamoto K, Nagano T, Okamoto R, Ibuki N, Tagashira M, Tsuji T: Immunohistochemical study on phenotypical changes of hepatocytes in liver disease with reference to extracellular matrix composition. Liver 19:32-38, 1999
Fukuda R, Ishimura N, Nguyen XT, Chowdhury A, Ishihara S, Sakai S, Akagi S, Tokuda A, Watanabe M, Fukumoto S: Gene expression of perforin and granzyme A in the liver in chronic hepatitis C: Comparison with peripheral blood mononuclear cells. Microbiol Immunol 39:873-877, 1995
Hiramatsu N, Hayashi N, Katayama K, Mochizuki K, Kawanishi Y, Kasahara A, Fusamoto H, Kamada T: Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C. Hepatology 19:1354-1359, 1994
Galle PR, Hofmann WJ, Walczak H, Schaller H, Otto G, Stremmel W, Krammer PH, Runkel L: Involvement of the CD95 (APO-1/ Fas) receptor and ligand in liver damage. J Exp Med 182:1223-1230, 1995
Mochizuki K, Hayashi M, Hiramatsu N, Katayama K, Kawanishi Y, Kasahara A, Fusamoto H, Kamada T: Fas antigen expression in liver tissues of patients with chronic hepatitis B. J Hepatol 24:1-7, 1996
Takatani M, Yamada G, Tsugeno H, Kishi F, Doi T, Yonehara S, Tsuji T: Immunohistochemical observation of Fas in the liver: Light and electron microscopic observation by immunoperoxidase method. Intern Hepatol Commun 4:334-342, 1996
Mita E, Hayashi N, Iio S, Takehara T, Hijioka T, Fusamoto H, Kamada T: Role of Fas ligand in apoptosis induced by hepatitis C virus infection. Biochem Biophys Res Commun 204:468-474, 1994
Mosnier J-F, Degott C, Marcellin P, Henin D, Erlinger S, Benhamou J-P: The intraportal lymphoid nodule and its environment in chronic active hepatitis C. Hepatology 17:366-371, 1993
Volpes R, van den Oord JJ, Desmet VJ: Immunohistochemical study of adhesion molecules in liver inflammation. Hepatology 12:59-65, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tagashira, M., Yamamoto, K., Fujio, K. et al. Expression of Perforin and Fas Ligand mRNA in the Liver of Viral Hepatitis. J Clin Immunol 20, 347–353 (2000). https://doi.org/10.1023/A:1006668013276
Issue Date:
DOI: https://doi.org/10.1023/A:1006668013276