Vadas P
Wellesley Hospital Research Institute, The Wellesley Central Hospital, University of Toronto, ON, Canada.
Biochim Biophys Acta. 1997 Jun 2;1346(2):193-7. doi: 10.1016/s0005-2760(97)00029-5.
Systemic inflammatory response syndromes including septic shock and salicylate poisoning are associated with high circulating levels of secretory phospholipase A2 (sPLA2). In septic shock, sPLA2 has been implicated in the pathogenesis of multisystem organ failure, presumably by a direct cytotoxic effect on cells. The cytotoxicity of recombinant human sPLA2 and a venom PLA2 were examined on human erythrocytes, erythroleukemia cells and U937 cells. Neither the human nor venom PLA2's were directly injurious to target cells. However, in the presence of liposomal phospholipids, both PLA2's induced irreversible cell injury. Whereas venom PLA2 was cytolytic in the presence of either phosphatidylcholine or phosphatidylethanolamine (PE), rh-sPLA2 caused cell death only in the presence of PE. These data show that normal unperturbed cells are resistant to injury from PLA2, and that additional cofactors such as PE are required to induce cell injury.
包括脓毒性休克和水杨酸盐中毒在内的全身炎症反应综合征与分泌型磷脂酶A2（sPLA2）的高循环水平相关。在脓毒性休克中，sPLA2可能通过对细胞的直接细胞毒性作用，参与多系统器官衰竭的发病机制。研究了重组人sPLA2和一种蛇毒PLA2对人红细胞、红白血病细胞和U937细胞的细胞毒性。人源和蛇毒PLA2均未对靶细胞造成直接损伤。然而，在脂质体磷脂存在的情况下，两种PLA2均诱导了不可逆的细胞损伤。蛇毒PLA2在磷脂酰胆碱或磷脂酰乙醇胺（PE）存在时具有细胞溶解作用，而重组人sPLA2仅在PE存在时导致细胞死亡。这些数据表明，正常未受干扰的细胞对PLA2损伤具有抗性，并且需要诸如PE等额外的辅助因子来诱导细胞损伤。
