Thematic Review Series: Phospholipases: Central Role in Lipid Signaling and Disease A new era of secreted phospholipase A2

Among more than 30 members of the phospholipase A(2) (PLA(2)) superfamily, secreted PLA(2) (sPLA(2)) enzymes represent the largest family, being Ca2+ -dependent low-molecular-weight enzymes with a His-Asp catalytic dyad. Individual sPLA(2)s exhibit unique tissue and cellular distributions and enzymatic properties, suggesting their distinct biological roles. Recent studies using transgenic and knockout mice for nearly a full set of sPLA(2) subtypes, in combination with sophisticated lipidomics as well as biochemical and cell biological studies, have revealed distinct contributions of individual sPLA(2)s to various pathophysiological events, including production of pro-and anti-inflammatory lipid mediators, regulation of membrane remodeling, degradation of foreign phospholipids in microbes or food, or modification of extracellular noncellular lipid components. In this review, we highlight the current understanding of the in vivo functions of sPLA(2)s and the underlying lipid pathways as revealed by a series of studies over the last decade.