Acute toxicity of an anti-Fas antibody in mice

By histopathologic examination of various organs in 3 normal strains, C3H/H eN, ICR, and DBA/1J, of mice treated intravenously once with anti-Fas antib ody (Jo2). we failed to determine any target organ, except the liver, respo nsible for the acute lethality induced by the Fas/anti-Fas antibody interac tion. However, we could show the presence of Fas-mediated apoptosis in othe r organs aside from the liver and normal mouse strain differences in suscep tibility to anti-Fas antibody. Among these strains, C3H/HeN was the most su sceptible to the antibody, followed by ICR and DBA/1J. We observed Fas-medi ated. apoptosis in the liver, spleen, thymus, Lymph nodes, Peyer's patch, i ntestine, skin, coagulation glands, ovary, uterus, and vagina in all 3 stra ins and additionally in the epididymides and seminal vesicles in the DBA/1J strain. We also demonstrated that Fas-mediated apoptosis of small lymphocy tes in the mantle zone of splenic lymphatic follicles preceded that of the hepatocytes or thymic cells. Since cellular damage was most severe in the l iver among all the apoptotic organs in the 3 mouse strains, liver injury in duced by anti-Fas antibody is speculated to play a significant role in the death.