LETHAL EFFECT OF THE ANTI-FAS ANTIBODY IN MICE
LETHAL EFFECT OF THE ANTI-FAS ANTIBODY IN MICE
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DOI：
10.1038/364806a0
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发表时间：
1993-08-26
期刊：
影响因子：
64.8
通讯作者：
NAGATA, S
中科院分区：
文献类型：
--
作者：
OGASAWARA, J;WATANABEFUKUNAGA, R;NAGATA, S
在哺乳动物的发育过程中，许多细胞被编程死亡1，2大多数由细胞凋亡介导3。Fas抗原4由小鼠淋巴细胞增殖突变（lpr）5，6的结构基因编码，是一种属于肿瘤坏死因子/神经生长因子受体家族7，8的细胞表面蛋白，并介导凋亡7。Fas抗原信使RNA在胸腺、肝脏、心脏、肺和卵巢中表达8。我们制备了一株抗小鼠Fas抗原的单克隆抗体，它与抗原（M（r）45 K）免疫沉淀，并对表达小鼠Fas抗原的细胞株具有细胞溶解活性。我们在这里报告，小鼠胸腺细胞的抗体染色表明，胸腺细胞从野生型和lpr（cg）小鼠表达Fas抗原，而很少的Fas抗原的表达被发现在lpr小鼠。小鼠腹腔注射抗Fas抗体可迅速杀死野生型小鼠，但lpr和lpr（cg）小鼠均未死亡。生化、组织学和电子显微镜分析表明，细胞凋亡对肝脏造成严重损害。这些结果表明，Fas抗原是重要的程序性细胞死亡在肝脏中，并可能参与在某些情况下，暴发性肝炎。
DURING mammalian development, many cells are programmed to die1,2 most mediated by apoptosis3. The Fas antigen4 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 family7,8, and mediates apoptosis7. The Fas antigen messenger RNA is expressed in the thymus, liver, heart, lung and ovary8. 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.