Contribution of Fas ligand to T cell-mediated hepatic injury in mice

Gastroenterology. 1997 Oct;113(4):1315-22. doi: 10.1053/gast.1997.v113.pm9322527.


Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Aspartate Aminotransferases / blood
  • Cells, Cultured
  • Concanavalin A / toxicity
  • DNA Primers
  • Fas Ligand Protein
  • Female
  • Hepatitis, Animal / immunology
  • Hepatitis, Animal / pathology*
  • Hepatitis, Animal / prevention & control
  • Liver / drug effects
  • Liver / immunology*
  • Liver / pathology*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, SCID
  • Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • fas Receptor / biosynthesis
  • fas Receptor / genetics
  • fas Receptor / physiology*


  • Antibodies, Monoclonal
  • DNA Primers
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • fas Receptor
  • Concanavalin A
  • Aspartate Aminotransferases
  • Alanine Transaminase