The Roles of the Secreted Phospholipase A(2) Gene Family in Immunology

Within the phospholipase A(2) (PLA(2)) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA(2) (sPLA(2)) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA(2)s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA(2) enzymes, particularly cytosolic PLA(2) (cPLA(2)α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA(2)s have remained a mystery over the last few decades. Recent studies employing mice gene-manipulated for individual sPLA(2)s, 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 sPLA(2)s in various immune responses and associated diseases.