The perturbed membrane of cells undergoing apoptosis is susceptible to type II secretory phospholipase A2 to liberate arachidonic acid.
Several lines of evidence have suggested that the plasma membranes of cells elicited by proinflammatory stimuli or microvesicles shed from activated cells are sensitive to extracellular type II secretory phospholipase A2 (sPLA2) that liberates fatty acids and lysophospholipids. Here we report that the membranes of cells undergoing apoptosis are highly susceptible to type II sPLA2. When neuronally differentiated rat pheochromocytoma PC12 cells deprived of nerve growth factor and serum, mouse mast cells deprived of hematopoietic cytokines or human monocytic U937 cells stimulated via Fas antigen (a receptor for the death factor Fas ligand), were exposed to type II sPLA2 at concentrations comparable to those detected at inflamed sites, the release of arachidonic acid was significantly accelerated in association with the process of programmed cell death. Arachidonic acid release by sPLA2 was dependent on the extracellular Ca2+ and was accompanied by preferential hydrolysis of phosphatidylethanolamine and phosphatidylserine in the membrane phospholipids. Association of sPLA2 with cell surface proteoglycan, which has been shown to be a prerequisite for endogenous sPLA2-dependent arachidonic acid release from the plasma membranes of live cells, was not essential for sPLA2-mediated hydrolysis of apoptotic cell membranes. Taking these results together, the apoptotic cell membrane is a potential target for extracellular type II sPLA2. The present findings may be relevant to events occurring at inflammatory or ischemic disease sites where apoptotic cells accumulate.
Atsumi
G
G
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Murakami
M
M
Tajima
M
M
Shimbara
S
S
Hara
N
N
Kudo
I
I
D000818:Animals; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology; D016716:PC12 Cells; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D051381:Rats; D019014:fas Receptor / Q000502:physiology
D016207:Cytokines; D009414:Nerve Growth Factors; D019014:fas Receptor; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2