Role of cytosolic phospholipase A2 in allergic response and parturition

Abstract

Phospholipase A₂ (PLA₂) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position^1,2,3. Among the members of this superfamily, cytosolic PLA₂ has attracted attention because it preferentially hydrolyses arachidonoyl phospholipids and is activated by submicromolar concentrations of Ca²⁺ ions and by phosphorylation by mitogen-activated protein kinases (MAP kinases)^4,5,6,7,8. Here we investigate the function of cytosolic PLA₂ in vivo by using homologous recombination to generate mice deficient in this enzyme. These mice showed a marked decrease in their production of eicosanoids and platelet-activating factor in peritoneal macrophages. Their ovalbumin-induced anaphylactic responses were significantly reduced, as was their bronchial reactivity to methacholine. Female mutant mice failed to deliver offspring, but these could be rescued by administration of a progesterone-receptor antagonist to the mother at term. Considered together with previous findings^{9,10,11,12,13,14,15}, our results indicate that cytosolic PLA₂ plays a non-redundant role in allergic responses and reproductive physiology.