The Roles of the Secreted Phospholipase A₂ Gene Family in Immunology

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.