Within the phospholipase A2 (PLA2) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA2 (sPLA2) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA2s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA2 enzymes, particularly cytosolic PLA2 (cPLA2α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA2s have remained a mystery over the last few decades. Recent studies employing mice gene-manipulated for individual sPLA2s, in combination with mass spectrometric lipidomics to identify their target substrates and products in vivo, have revealed their roles in diverse biological events, including immunity and associated disorders, through lipid mediator-dependent or -independent processes in given microenvironments. In this review, we summarize our current knowledge of the roles of sPLA2s in various immune responses and associated diseases.
Keywords: Arachidonic acid; Docosahexaenoic acid; Eicosanoid; Fatty acid; Leukotriene; Lysophospholipid; Membrane; Phospholipase A(2); Phospholipid; Prostaglandin.
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