THE PERTURBED MEMBRANE OF CELLS UNDERGOING APOPTOSIS IS SUSCEPTIBLE TO TYPE-II SECRETORY PHOSPHOLIPASE A(2) TO LIBERATE ARACHIDONIC-ACID

Several lines of evidence have suggested that the plasma membranes of cells elicited by proinflammatory stimuli or microvesicles shed from a ctivated cells are sensitive to extracellular type II secretory phosph olipase A(2) (sPLA(2)) that liberates fatty acids and lysophospholipid s. Here we report that the membranes of cells undergoing apoptosis are highly susceptible to type LT sPLA(2). When neuronally differentiated rat pheochromocytoma PC12 cells deprived of nerve growth factor and s erum, mouse mast cells deprived of hematopoietic cytokines or human mo nocytic U937 cells stimulated via Fas antigen (a receptor for the deat h factor Fas ligand), were exposed to type II sPLA(2) at concentration s comparable to those detected at inflamed sites, the release of arach idonic acid was significantly accelerated in association with the proc ess of programmed cell death. Arachidonic acid release by sPLA(2) was dependent on the extracellular Ca2+ and was accompanied by preferentia l hydrolysis of phosphatidylethanolamine and phosphatidylserine in the membrane phospholipids. Association of sPLA(2) with cell surface prot eoglycan, which has been shown to be a prerequisite for endogenous sPL A(2)-dependent arachidonic acid release from the plasma membranes of l ive cells, was not essential for sPLA(2)-mediated hydrolysis of apopto tic cell membranes. Taking these results together, the apoptotic cell membrane is a potential target for extracellular type II sPLA(2). The present findings may be relevant to events occurring at inflammatory o r ischemic disease sites where apoptotic cells accumulate. (C) 1997 El sevier Science B.V.