ROLE OF CYTOSOLIC PHOSPHOLIPASE A(2) IN ALLERGIC RESPONSE AND PARTURITION

Phospholipase A(2) (PLA(2)) comprises a superfamily of enzymes that hy drolyse the ester bond of phospholipids at the sn-2 position(1-3). Amo ng the members of this superfamily, cytosolic PLA(2) has attracted att ention 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)(4-8 ). Here we investigate the function of cytosolic PLA(2) in vivo by usi ng homologous recombination to generate mice deficient in this enzyme. These mice showed a marked decrease in their production of eicosanoid s and platelet-activating factor in peritoneal macrophages. Their oval bumin-induced anaphylactic responses were significantly reduced, as wa s their bronchial reactivity to methacholine. Female mutant mice faile d to deliver offspring, but these could be rescued by administration o f a progesterone-receptor antagonist to the mother at term. Considered together with previous findings(9-15), our results indicate that cyto solic PLA(2) plays a non-redundant role in allergic responses and repr oductive physiology.