A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis

A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis
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DOI:
10.1073/pnas.95.11.6290
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发表时间:
1998-05-26
影响因子:
11.1
通讯作者:
Schlossman, SF
Schlossman, SF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang, CG;Xu, YH;Schlossman, SF

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细胞死亡是由不同的途径介导的,包括细胞凋亡和细胞胀亡,以响应各种死亡信号。为了表征参与细胞死亡的分子,通过用凋亡细胞免疫小鼠来产生一组mAb。发现这些抗体中的一种,称为抗Porimin(用于诱导膜损伤的原癌细胞受体),直接诱导Jurkat细胞中的独特类型的细胞死亡。Anti-Porimin定义了Jurkat细胞上的110-kDa细胞表面受体。在功能上,单独的抗Porimin快速介导质膜上的孔形成并诱导细胞死亡,而不需要补体的参与。Porimin抗原的细胞表达和功能特征表明它不同于CD 95(Fas/Apo-1)和已知诱导凋亡的其他细胞受体。抗Porimin介导的细胞死亡之前,细胞聚集,质膜孔的形成,和膜泡的外观。更重要的是,这些细胞既不显示DNA片段化,也不显示凋亡小体,但显示细胞膜的致命损伤。由抗Porimin引起的细胞死亡不同于补体依赖性细胞溶解或补体非依赖性细胞凋亡,但与所描述的细胞胀亡相似,细胞胀亡是一种伴随膜损伤随后核溶解的细胞死亡形式。抗Porimin诱导细胞死亡可能代表了人类淋巴系统中独特的细胞表面受体介导的细胞死亡途径。
Cell death is mediated by distinct pathways including apoptosis and oncosis in response to various death signals. To characterize molecules involved in cell death, a panel of mAbs was raised by immunizing mice with apoptotic cells. One of these antibodies, designated anti-Porimin (for pro-oncosis receptor inducing membrane injury), was found to directly induce a unique type of cell death in Jurkat cells. Anti-Porimin defines a 110-kDa cell surface receptor on Jurkat cells. Functionally, anti-Porimin alone rapidly mediates pore formation on the plasma membrane and induces cell death without participation of complement. Both the cellular expression and functional characteristics of the Porimin antigen indicate that it is distinct from the CD95 (Fas/Apo-1) and other cell receptors known to induce apoptosis. Anti-Porimin-mediated cell death was preceded by cell aggregation, formation of plasma membrane pores, and the appearance of membrane blebs. More important, these cells show neither DNA fragmentation nor apoptotic bodies, but display lethal damage of the cell membrane. Cell death by anti-Porimin is distinct from complement-dependent cytolysis or complement-independent apoptosis but is similar to that described for oncosis, a form of cell death accompanied by the membrane damage followed by karyolysis. The induction of cell death by anti-Porimin may represent a unique cell surface receptor-mediated pathway of cell death in the human lymphoid system.