Regulatory functions of phospholipase A₂

Phospholipase A₂ (PLA₂) plays crucial roles in diverse cellular responses, including phospholipid digestion and metabolism, host defense and signal transduction. PLA₂ provides precursors for generation of eicosanoids, such as prostaglandins (PGs) and leukotrienes (LTs), when the cleaved fatty acid is arachidonic acid, platelet-activating factor (PAF) when the sn-1 position of the phosphatidylcholine contains an alkyl ether linkage and some bioactive lysophospholipids, such as lysophosphatidic acid (lysoPA). As overproduction of these lipid mediators causes inflammation and tissue disorders, it is extremely important to understand the mechanisms regulating the expression and functions of PLA₂. Recent advances in molecular and cellular biology have enabled us to understand the molecular nature, possible function, and regulation of a variety of PLA₂ isozymes. Mammalian tissues and cells generally contain more than one enzyme, each of which is regulated independently and exerts distinct functions. Here we classify mammalian PLA₂ S into three large groups, namely, secretory (sPLA₂), cytosolic (cPLA₂), and Ca²⁺-independent PLA₂s, on the basis of their enzymatic properties and structures and focus on the general understanding of the possible regulatory functions of each PLA₂ isozyme. In particular, the roles of type II sPLA₂ and cPLA₂ in lipid mediator generation are discussed.