Induction of group II phospholipase A2 expression and pathogenesis of the sepsis syndrome

Phospholipase A2 catalysed hydrolysis of phospholipid substrates is rate-limiting in the release of arachidonic acid for subsequent downstream metabolism to biologically active eicosanoids. Concomitant release of lysoplatelet activating factor (lyso PAF) serves as the precursor of PAF. Thus, phospholipase A2 (PLA2) is pivotal in the generation of a spectrum of biologically active lipids. Over the course of the past decade, studies have increasingly pointed to a pathogenetic association between endotoxin-induced PLA2 expression and ensuing circulatory shock and multisystem organ failure in animals with experimental endotoxemia as well as in patients with septic shock. The structural, functional, regulatory and biologic characteristics of PLA2 are reviewed in relation to septic shock and its complications and areas of controversy are highlighted.