Group II phospholipases A2 are indirectly cytolytic in the presence of exogenous phospholipid.
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.
Vadas
P
P
Wellesley Hospital Research Institute, The Wellesley Central Hospital, University of Toronto, ON, Canada.
D002470:Cell Survival / Q000187:drug effects*; D002857:Chromium / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D054501:Group II Phospholipases A2; D006461:Hemolysis; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010741:Phospholipases A / Q000097:blood / Q000633:toxicity*; D054467:Phospholipases A2; D010743:Phospholipids / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000633:toxicity; D012910:Snake Venoms / Q000201:enzymology; D014407:Tumor Cells, Cultured
D008246:Lysophospholipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011994:Recombinant Proteins; D012910:Snake Venoms; D002857:Chromium; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2