Acute toxicity of an anti-Fas antibody in mice.
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.
Kakinuma
C
C
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan.
Takagaki
K
K
Yatomi
T
T
Nakamura
N
N
Nagata
S
S
Uemura
A
A
Shibutani
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006066:Gonads / Q000187:drug effects / Q000473:pathology; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor