Lethal effect of the anti-Fas antibody in mice

• Published in: Nature (London) 1993-08, Vol.364 (6440), p.806-809
• Main Authors: Ogasawara, Jun, Watanabe-Fukunaga, Rie, Adachi, Masashi, Matsuzawa, Akio, Kasugai, Tsutomu, Kitamura, Yukihiko, Itoh, Naoto, Suda, Takashi, Nagata, Shigekazu
• Format: Article
• Language: English
• Subjects: Ageing, cell death; Animals; Antibiotics; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - toxicity; Antigens, Surface - biosynthesis; Antigens, Surface - genetics; Antigens, Surface - immunology; Antigens, Surface - physiology; Apoptosis - physiology; Biological and medical sciences; Blood; Cell Line; Cell physiology; Cricetinae; fas Receptor; Female; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; Hybrid Cells; Immunity (Disease); letter; Liver - metabolism; Liver - ultrastructure; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Molecular and cellular biology; multidisciplinary; Mutation; Myocardium - ultrastructure; Phagocytosis; Rodents; Science; Science (multidisciplinary); Thymus Gland - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/364806a0

DURING mammalian development, many cells are programmed to die 1,2 most mediated by apoptosis 3 . The Fas antigen 4 coded by the structural gene for mouse lymphoproliferation mutation ( lpr ) 5,6 , is a cell surface protein belonging to the tumour necrosis factor/nerve growth factor receptor family 7,8 , and mediates apoptosis 7 . The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary 8 . 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 lpr cg 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 lpr cg 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.