Emerging roles of secreted phospholipase A2 enzymes: Lessons from transgenic and knockout mice

Among the emerging phospholipase A(2) (PLA(2)) superfamily, the secreted PLA(2) (sPLA(2)) family consists of low-molecular-mass, Ca(2+)-requiring extracellular enzymes with a His-Asp catalytic dyad. To date, more than 10 sPLA(2) enzymes have been identified in mammals. Individual sPLA(2)s exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Despite numerous enzymatic and cell biological studies on this enzyme family in the past two decades, their precise in vivo functions still remain largely obscure. Recent studies using transgenic and knockout mice for several sPLA(2) enzymes, in combination with lipidomics approaches, have opened new insights into their distinct contributions to various biological events such as food digestion, host defense, inflammation, asthma and atherosclerosis. In this article, we overview the latest understanding of the pathophysiological functions of individual sPLA(2) isoforms fueled by studies employing transgenic and knockout mice for several sPLA(2)s.