ABSTRACT
Phospholipase A2 (PLA2) is a group of enzymes that liberate a fatty acid and a lysophospholipid from a glycerophospholipid, a major component in cell membranes. The PLA2 reaction is considered as the ™rst rate-limiting step for the production of lipid mediators derived from arachidonic acid (AA) or lysophospholipids, such as eicosanoids [prostaglandins (PGs) and leukotrienes (LTs)] and platelet-activating factor (PAF). Mammalian genomes encode a number of PLA2 enzymes, which are subdivided into several subclasses based on their structures, localizations, and functions. Of these, cytosolic PLA2 (cPLA2α) group IVA and secreted PLA2s (sPLA2s) group V and X have attracted much attention as regulators of the pathology in airway disorders. No doubt, cPLA2α is a central player of AA release that globally provides airway eicosanoids, whereas sPLA2s are likely to participate in spatiotemporal production of lipid mediators or in degradation of pulmonary surfactant, a noncellular phospholipid component essential for airway homeostasis and stability. Perturbation of the cPLA2α-and sPLA2-dependent pathways causes detrimental airway disorders. In this chapter, we will highlight the basic biology of PLA2s and their potential contributions to airway diseases on the basis of recent ™ndings by pharmacological,
3.1 Basic Biology of Phospholipase A2 Enzymes ................................................. 42 3.2 Evidence for the Roles of PLA2 Enzymes in Airway InŠammation ..............46
