Role of phospholipases and oxidized phospholipids in inflammation

Abstract

Long thought of as a bystander in pathophysiological processes, lipid molecules have emerged as bioactive mediators of cellular activity. Oxidized phospholipids (OxPLs), generated during enzymatic and non-enzymatic processes, modulate cellular processes through receptor-mediated pathways that can effect a whole host of activities including apoptosis, monocyte adhesion, platelet aggregation, and regulation of immune responses. Initially discovered as platelet activating factor analogs, there have been close to 50 distinct OxPL molecules that have been identified within biological tissues. With the advent of robust analytical systems, we are better able to identify and quantitate these molecules in an ever growing list of different biological tissues which has allowed for the generation of a comprehensive oxolipid profiles in both normal and disease states. Given the increased affinity of phospholipases towards OxPLs we are in the early stages of understanding of the complex interplay between the modification of OxPL through phospholipase activity and the cellular responses to the released hydrolyzed products. In this review we will summarize the role of OxPL in different pathological states and the specific phospholipases that have been shown to interact with OxPLs.