CONTRIBUTION OF FAS LIGAND TO T-CELL-MEDIATED HEPATIC-INJURY IN MICE

Background & Aims: Fas has been implicated in liver damage, The aim of this study was to investigate the role of its ligand to induce hepato cyte death and liver damage in T cell-dependent hepatitis, Methods: Fa s 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 iso lated hepatocytes from wild-type or gld mice, but not those from lpr m ice, were susceptible to Fas ligand-mediated lysis, When concanavalin A was intravenously administered into wild-type mice, they developed a cute hepatic injury with massive degenerative changes in hepatocytes, In contrast, both gld and lpr mice had lower aminotransferase levels w ith milder histological changes, Reverse-transcription polymerase chai n reaction and flow cytometric analysis showed that Fas ligand was ind uced in the liver shortly after the concanavalin A injection and was p redominantly expressed on intrahepatic T cells, Administration of mono clonal antibody neutralizing mouse Fas ligand could reduce the aminotr ansferase increase, Conclusions: The results indicate that Fas ligand plays a role in the T cell-dependent hepatitis induced by concanavalin A administration.