CD95-mediated apoptosis in vivo involves acid sphingomyelinase.
CD95-mediated apoptosis in vivo involves acid sphingomyelinase.
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DOI：
10.1074/jbc.m002957200
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发表时间：
2000-09
期刊：
影响因子：
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通讯作者：
Susanne Kirschnek;Francois Paris;Michael Weller;H. Grassmé;K. Ferlinz;Andrea Riehle;Zvi Fuks;
中科院分区：
文献类型：
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作者：
Susanne Kirschnek;Francois Paris;Michael Weller;H. Grassmé;K. Ferlinz;Andrea Riehle;Zvi Fuks;
酸性鞘磷脂酶（ASM）在应激诱导的细胞凋亡中具有重要作用，但其在受体诱导的细胞凋亡中的生理功能尚不清楚。在这里，我们描绘了一个关键的作用，ASM在CD 95触发的外周淋巴细胞或肝细胞在体内的凋亡。我们采用静脉注射抗CD 4抗体或植物血凝素，这是以前显示，通过内源性CD 95/CD 95配体系统导致外周血淋巴细胞或肝细胞凋亡。我们的研究结果表明，在正常小鼠的易感性高，而ASM敲除小鼠未能免疫耗竭T细胞或发展自身免疫样肝炎。同样，ASM缺陷小鼠或离体肝细胞和脾细胞表现出对抗CD 95治疗的抗性。这些结果为ASM在CD 95诱导的细胞凋亡中的重要生理功能提供了体内证据。
Acid sphingomyelinase (ASM) is reported to have an essential function in stress-induced apoptosis although the physiological function of ASM in receptor-triggered apoptosis is unknown. Here, we delineate a pivotal role for ASM in CD95-triggered apoptosis of peripheral lymphocytes or hepatocytes in vivo. We employed intravenous injection of anti-CD4 antibodies or phytohemagglutinin that was previously shown to result in apoptosis of peripheral blood lymphocytes or hepatocytes via the endogenous CD95/CD95 ligand system. Our results demonstrate a high susceptibility in normal mice whereas ASM knock-out mice fail to immunodeplete T cells or develop autoimmune-like hepatitis. Likewise, ASM-deficient mice or hepatocytes and splenocytes ex vivo manifest resistance to anti-CD95 treatment. These results provide in vivo evidence for an important physiological function of ASM in CD95-induced apoptosis.