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Acute Toxicity of an Anti-Fas Antibody in Mice
Chihaya Kakinuma
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., 342 Gensuke, Fujieda, Shizuoka 426-8640, Japan
Kinya Takagaki
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., 342 Gensuke, Fujieda, Shizuoka 426-8640, Japan
Takehwo Yatomi
Bioscience Laboratory, Mochida Pharmaceutical Co., Ltd., 1-1-1 Kamiya, Kita-ku, Tokyo 115-8515, Japan
Norio Nakamura
Bioscience Laboratory, Mochida Pharmaceutical Co., Ltd., 1-1-1 Kamiya, Kita-ku, Tokyo 115-8515, Japan
Shigekazu Nagata
Department of Genetics, Osaka University Medical School B3, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
Akio Uemura
Bioscience Laboratory, Mochida Pharmaceutical Co., Ltd., 1-1-1 Kamiya, Kita-ku, Tokyo 115-8515, Japan
Yasunori Shibutani
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., 342 Gensuke, Fujieda, Shizuoka 426-8640, Japan
By histopathologic examination of various organs in 3 normal strains, C3H/HeN, ICR, and DBA/1J, of mice treated intravenously once with anti-Fas antibody (Jo2), we failed to determine any target organ, except the liver, responsible for the acute lethality induced by the Fas/anti-Fas antibody interaction. However, we could show the presence of Fas-mediated apoptosis in other organs aside from the liver and normal mouse strain differences in susceptibility to anti-Fas antibody. Among these strains, C3H/HeN was the most susceptible to the antibody, followed by ICR and DBA/1J. We observed Fas-mediated apoptosis in the liver, spleen, thymus, lymph nodes, Peyer's patch, intestine, skin, coagulation glands, ovary, uterus, and vagina in all 3 strains and additionally in the epididymides and seminal vesicles in the DBA/1J strain. We also demonstrated that Fas-mediated apoptosis of small lymphocytes in the mantle zone of splenic lymphatic follicles preceded that of the hepatocytes or thymic cells. Since cellular damage was most severe in the liver among all the apoptotic organs in the 3 mouse strains, liver injury induced by anti-Fas antibody is speculated to play a significant role in the death.
Key Words: Anti-Fas antibody • Jo2 • acute toxicity • pathology • apoptosis • mice
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Toxicologic Pathology, Vol. 27, No. 4,
412-420 (1999)
DOI: 10.1177/019262339902700404
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