Phospholipase A2 enzymes: Potential targets for therapy

Abstract

The endothelial cells lining blood vessels control vascular tone and actively participate in the inflammatory process by recruiting circulating cells to the underlying tissue. Activation of endothelial cell phospholipase A2 (PLA2) results in enhanced membrane phospholipid hydrolysis, leading to free fatty acid and lyso- phospholipid production. Arachidonic acid is further metabolized into eicosanoids, and lysophospholipids can be acetylated to form platelet-activating factor (PAF). Endothelial cells can release vasodilator or constrictor prostaglandins depending on the stimulus involved thereby regulating the vascular tone and local blood flow. Recruitment of inflammatory cells is mediated by endothelial cell PAF production. We have determined that endothelial cell PAF production is dependent upon iPLA2B- mediated phospholipid hydrolysis and we propose that selective inhibition of this enzyme could be of potential therapeutic value for inflammatory diseases in the future. This review offers a discussion of activation and inhibition of PLA2 enzymes and further focuses on our more recent studies that highlight endothelial cell iPLA2B activation and the implication for inflammatory disease management.