Specific physiological roles of cytosolic phospholipase A₂ as defined by gene knockouts

The cytosolic 85 kDa phospholipase A₂ (cPLA₂) is a unique member of the phospholipase A₂ (PLA₂) superfamily. Because PLA₂ activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA₂ (cPLA₂(-/-) mouse). cPLA₂(-/-) mice develop normally but the females have severe reproductive defects. cPLA₂(-/-) mice suffer smaller infarcts and fewer neurological deficits after transient occlusion of the middle cerebral artery and have less injury after administration of a dopaminergic selective neurotoxin. cPLA₂(-/-) mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from cPLA₂(-/-) mice fail to produce prostaglandins, leukotriene B₄ and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA₂(-/-) mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA₂ knockout mouse has revealed important roles of cPLA₂ in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA₂(-/-) mouse reveals that the many other forms of PLA₂ cannot replace many functions of cPLA₂. The importance of cPLA₂ in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits. (C) 2000 Elsevier Science B.V.