Role of Phospholipases A2 Inflammation

Abstract

Phospholipase A2 (PLA2) comprises a group of lipolytic enzymes that specifically release fatty acids, often arachidonic acid, from the sn-2 position of membrane phospholipids for the production of important lipid mediators such as prostaglandins, leukotrienes, and platelet activating factor (van den Bosch, 1980; Glaser et al., 1993; Mayer and Marshall, 1993; Kudo et al., 1993). Arachidonic acid and its numerous metabolites act as intracellular and intercellular messengers, contributing to normal cellular physiology by modifying the activity of intracellular enzymes and ion channels. Moreover, PLA2 and its products function as substrates for the generation of inflammatory lipid mediators that play an important role in the pathogenesis of inflammatory diseases (Vadas and Pruzanski, 1986; Pruzanski and Vadas, 1991). The level of free intracellular arachidonic acid is extremely low, and in most tissues and cells the synthesis of eicosanoids is limited by the availability of free arachidonic acid. The major mechanisms usually considered to control the level of intracellular free arachidonic acid in most cell types is the activation of PLA2 enzymes are ubiquitously expressed and thus can be found in nearly all cell types examined, as well as in bacteria protozoa. In recent years, it has become evident that PLA2s are a heterogeneous family of enzymes that can be divided into main classes based on their molecular mass and cellular distribution (Dennis, 1997). The class of low molecular weight secreted PLA2s (sPLA2s) and the high molecular weight cytosolic PLA2s (cPLA2s) which is subdivided into a Ca2+ -dependent and Ca2+ -independent group.