Zhang C, Xu Y, Gu J, Schlossman S F
Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6290-5. doi: 10.1073/pnas.95.11.6290.
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.
细胞死亡是由不同的途径介导的,包括凋亡和胀亡,以响应各种死亡信号。为了鉴定参与细胞死亡的分子,用凋亡细胞免疫小鼠制备了一组单克隆抗体。其中一种抗体,命名为抗孔蛋白(促胀亡受体诱导膜损伤),被发现可直接在Jurkat细胞中诱导一种独特类型的细胞死亡。抗孔蛋白鉴定出Jurkat细胞上一种110 kDa的细胞表面受体。在功能上,单独的抗孔蛋白可迅速介导质膜上形成孔道,并诱导细胞死亡,无需补体参与。孔蛋白抗原的细胞表达和功能特性均表明,它与CD95(Fas/Apo-1)及其他已知可诱导凋亡的细胞受体不同。抗孔蛋白介导的细胞死亡之前会出现细胞聚集、质膜孔道形成和膜泡的出现。更重要的是,这些细胞既不显示DNA片段化,也不出现凋亡小体,而是表现出细胞膜的致命损伤。抗孔蛋白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凋亡,但类似于胀亡,胀亡是一种细胞死亡形式,伴有膜损伤,随后是核溶解。抗孔蛋白诱导的细胞死亡可能代表了人类淋巴系统中一种独特的细胞表面受体介导的细胞死亡途径。