title: Contribution of Fas ligand to T cell-mediated hepatic injury in mice.
abstract: 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.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Seino
authors.forename: N
authors.initials: N
authors.lastname: Kayagaki
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Fukao
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: H
authors.initials: H
authors.lastname: Yagita
mesh_terms: 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*
chemical_list: 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