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Lethal effect of the anti-Fas antibody in mice
J Ogasawara1, R Watanabe-Fukunaga, M Adachi
1Osaka Bioscience Institute, Japan.
Abstract:
During mammalian development, many cells are programmed to die most mediated by apoptosis. The Fas antigen coded by the structural gene for mouse lymphoproliferation mutation (lpr), is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family, and mediates apoptosis. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary. We prepared a monoclonal antibody against mouse Fas antigen, which immunoprecipitated the antigen (M(r) 45K) and had cytolytic activity against cell lines expressing mouse Fas antigen. We report here that staining of mouse thymocytes with the antibody indicated that thymocytes from the wild-type and lprcg mice expressed the Fas antigen, whereas little expression of the Fas antigen was found in lpr mice. Intraperitoneal administration of the anti-Fas antibody into mice rapidly killed the wild-type mice but neither lpr nor lprcg mice. Biochemical, histological and electron microscope analyses indicated severe damage of the liver by apoptosis. These findings suggest that the Fas antigen is important in programmed cell death in the liver, and may be involved in fulminant hepatitis in some cases.
Insights
The Fas antigen mediates programmed cell death in mammals. Anti-Fas antibody induced rapid death in wild-type mice, highlighting Fas
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Apoptosis, or programmed cell death, is crucial during mammalian development.
- The Fas antigen, a cell surface protein in the TNF/NGF receptor family, mediates apoptosis.
- Fas antigen mRNA is expressed in various tissues, including thymus, liver, and ovary.
Purpose of the Study:
- To investigate the role of Fas antigen in programmed cell death.
- To characterize a monoclonal antibody against the mouse Fas antigen.
- To explore the involvement of Fas antigen in liver apoptosis and hepatitis.
Main Methods:
- Preparation of a monoclonal antibody against mouse Fas antigen.
- Immunoprecipitation and cytolytic activity assays.
- Staining of mouse thymocytes and intraperitoneal administration of anti-Fas antibody.
- Biochemical, histological, and electron microscope analyses of liver damage.
Main Results:
- The monoclonal antibody immunoprecipitated a 45K M(r) Fas antigen and showed cytolytic activity.
- Wild-type and lprcg mice thymocytes expressed Fas antigen, while lpr mice showed minimal expression.
- Intraperitoneal anti-Fas antibody administration caused rapid death in wild-type mice but not in lpr or lprcg mice.
- Severe liver damage due to apoptosis was observed in treated wild-type mice.
Conclusions:
- The Fas antigen plays a significant role in programmed cell death, particularly in the liver.
- Fas-mediated apoptosis may contribute to fulminant hepatitis.
- The developed anti-Fas antibody is a valuable tool for studying Fas-mediated apoptosis.
