Integrated Lipidomics in the Secreted Phospholipase A2 Biology

Mammalian genomes encode genes for more than 30 phospholipase A2s (PLA2s) or related enzymes, which are subdivided into several subgroups based on their structures, catalytic mechanisms, localizations and evolutionary relationships. More than one third of the PLA2 enzymes belong to the secreted PLA2 (sPLA2) family, which consists of low-molecular-weight, Ca2+-requiring extracellular enzymes, with a His-Asp catalytic dyad. Individual sPLA2 isoforms exhibit unique tissue and cellular localizations and enzymatic properties, suggesting their distinct pathophysiological roles. Recent studies using transgenic and knockout mice for several sPLA2 isoforms, in combination with lipidomics approaches, have revealed their distinct contributions to various biological events. Herein, we will describe several examples of sPLA2-mediated phospholipid metabolism in vivo, as revealed by integrated analysis of sPLA2 transgenic/knockout mice and lipid mass spectrometry. Knowledge obtained from this approach greatly contributes to expanding our understanding of the sPLA2 biology and pathophysiology