Lethal effect of the anti-Fas antibody in mice
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.
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Fas-mediated apoptosis is also reduced, as judged by using the monoclonal antibody Jo2 that recognizes and activates the Fas receptor and induces hepatic apoptosis, or by using ethanol gavage in mice, a system that mimics binge drinking in humans and triggers FasL-induced hepatocyte apoptosis.
“Fas-mediated apoptosis is also reduced, as judged by using the monoclonal antibody Jo2 that recognizes and activates the Fas receptor and induces hepatic apoptosis [109], or by using ethanol gavage in mice, a system that mimics binge drinking in humans and triggers FasL-induced hepatocyte apoptosis [110].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [109]
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- Authors
- Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- The University of Osaka (JP)
- ORCID
- Nagata, Shigekazu
- Venue
- Nature
- Published
- 1993-08
- Volume
- 364
- Issue
- 6440
- Pages
- 806-809
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2067534266
- Cited by
- 1,881
- References
- 29
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 13 · 2020: 19 · 2019: 21 · 2018: 25 · 2017: 29 · 2016: 17 · 2015: 29 · 2014: 32 · 2013: 37 · 2012: 39
- FWCI
- 24.97
- Type
- journal article
- Language
- en
- Update notices
- correction (1993-10-07)
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- Fas antigen, anti-Fas antibody, apoptosis, programmed cell death, lpr mutation, thymocytes, liver injury, fulminant hepatitis, cytotoxicity, TNF receptor superfamily, mouse lethality
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Surface, Blood, Cell Line, Female, Cricetinae, Humans, Hybrid Cells, Liver, Mice, Inbred BALB C, Mice, Inbred C3H, Mutation, Myocardium, Phagocytosis, Thymus Gland, Apoptosis, fas Receptor, Mice
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