Contribution of Fas ligand to T cell-mediated hepatic injury in mice.
OBJECTIVE
Fas has been implicated in liver damage. The aim of this study was to investigate the role of its ligand to induce hepatocyte death and liver damage in T cell-dependent hepatitis.


METHODS
Fas ligand-mediated lysis of primary hepatocytes from C57BL/6 wild-type, Fas ligand-deficient gld, and Fas-deficient lpr mice and concanavalin A-induced hepatitis in these mice were assessed.


RESULTS
Freshly isolated hepatocytes from wild-type or gld mice, but not those from lpr mice, were susceptible to Fas ligand-mediated lysis. When concanavalin A was intravenously administered into wild-type mice, they developed acute hepatic injury with massive degenerative changes in hepatocytes. In contrast, both gld and lpr mice had lower aminotransferase levels with milder histological changes. Reverse-transcription polymerase chain reaction and flow cytometric analysis showed that Fas ligand was induced in the liver shortly after the concanavalin A injection and was predominantly expressed on intrahepatic T cells. Administration of monoclonal antibody neutralizing mouse Fas ligand could reduce the aminotransferase increase.


CONCLUSIONS
The results indicate that Fas ligand plays a role in the T cell-dependent hepatitis induced by concanavalin A administration.
Seino
K
K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Kayagaki
N
N
Takeda
K
K
Fukao
K
K
Okumura
K
K
Yagita
H
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D002478:Cells, Cultured; D003208:Concanavalin A / Q000633:toxicity; D017931:DNA Primers; D053222:Fas Ligand Protein; D005260:Female; D006520:Hepatitis, Animal / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D003208:Concanavalin A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase