Role of cytosolic phospholipase A 2 in allergic response and parturition

• Published in: Nature (London) 1997-12, Vol.390 (6660), p.618-622
• Main Authors: Shimizu, Takao, Uozumi, Naonori, Kume, Kazuhiko, Nagase, Takahide, Nakatani, Noriaki, Ishii, Satoshi, Tashiro, Fumi, Komagata, Yoshinori, Maki, Kazushige, Ikuta, Koichi, Ouchi, Yasuyoshi, Miyazaki, Jun-ichi
• Format: Article
• Language: English
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/37622

Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position. 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). 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, our results indicate that cytosolic PLA2 plays a non-redundant role in allergic responses and reproductive physiology.