Protective effects of HFE7A, mouse anti-human/mouse Fas monoclonal antibody against acute and lethal hepatic injury induced by Jo2
- 19 December 2009
- journal article
- jaact special-issue
- Published by Springer Science and Business Media LLC in Cytotechnology
- Vol. 62 (4), 313-323
- https://doi.org/10.1007/s10616-009-9244-6
Abstract
HFE7A is a mouse anti-human/mouse Fas monoclonal antibody which, protects mice from fulminant hepatitis induced by Jo2. Herein, we report on the mechanism of the protective effect of HFE7A against Jo2-induced acute and lethal hepatic injury. HFE7A reduced the serum aminotransferase level which was elevated after Jo2 injection. HFE7A also inhibited caspase activation and mitochondrial depolarization in hepatocytes derived from apoptosis induced by Jo2 injection. The protective effect of HFE7A against Jo2-induced apoptosis in mouse hepatocytes was reproducible in vitro. The cell death and caspase activation in isolated mouse hepatocytes were induced by incubating these cells with Jo2 in vitro, and HFE7A inhibited the cell death and caspase activation in mouse hepatocytes in a dose-dependent manner. The affinity of HFE7A to mouse Fas was lower than that of Jo2. The binding of Jo2 to neither recombinant mouse Fas nor mouse hepatocytes was inhibited by an excessive amount of HFE7A. Interestingly, HFE7A bound to hepatocytes isolated from Fas knockout mice. From these results, it is suggested that HFE7A may exert a protective effect against Jo2-induced hepatitis not by competitively inhibiting the binding of Jo2 to Fas on hepatocytes, and that a distinct molecule other than Fas may possibly be involved in the protective effect of HFE7A against Jo2-induced hepatic injury.Keywords
This publication has 32 references indexed in Scilit:
- Ibuprofen administration attenuates serum TNF-α levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulationToxicology and Applied Pharmacology, 2008
- The Aryl Hydrocarbon Receptor Predisposes Hepatocytes to Fas-Mediated ApoptosisMolecular Pharmacology, 2004
- Anti-CD95-induced Lethality Requires Radioresistant FcγRII+ Cells: A NOVEL MECHANISM FOR FULMINANT HEPATIC FAILUREPublished by Elsevier BV ,2003
- Dominant negative MORT1/FADD rescues mice from CD95 and TNF-induced liver failureHepatology, 2003
- Cloning and Expression of a Novel Murine Anti-human Fas AntibodyBioscience, Biotechnology, and Biochemistry, 2000
- Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.JCI Insight, 1996
- Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome cCell, 1996
- Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liverNature Genetics, 1995
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- Mechanisms and Functions of Cell DeathAnnual Review of Cell Biology, 1991