Role of cytosolic phospholipase A2 in allergic response and parturition

Naonori Uozumi, Kazuhiko Kume, Takahide Nagase, Noriaki Nakatani, Satoshi Ishii, Fumi Tashiro, Yoshinori Komagata, Kazushige Maki, Koichi Ikuta, Yasuyoshi Ouchi, Jun-ichi Miyazaki and Takao Shimizu ()
Additional contact information
Naonori Uozumi: Geriatrics, Faculty of Medicine, University of Tokyo
Kazuhiko Kume: Geriatrics, Faculty of Medicine, University of Tokyo
Takahide Nagase: Faculty of Medicine, University of Tokyo
Noriaki Nakatani: Geriatrics, Faculty of Medicine, University of Tokyo
Satoshi Ishii: Geriatrics, Faculty of Medicine, University of Tokyo
Fumi Tashiro: Institute of Development, Aging and Cancer, Tohoku University
Yoshinori Komagata: Institute of Development, Aging and Cancer, Tohoku University
Kazushige Maki: Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, University of Tokyo
Koichi Ikuta: Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, University of Tokyo
Yasuyoshi Ouchi: Faculty of Medicine, University of Tokyo
Jun-ichi Miyazaki: Institute of Development, Aging and Cancer, Tohoku University
Takao Shimizu: Geriatrics, Faculty of Medicine, University of Tokyo

Nature, 1997, vol. 390, issue 6660, 618-622

Abstract: Abstract Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position1,2,3. 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 findings9,10,11,12,13,14,15, our results indicate that cytosolic PLA2 plays a non-redundant role in allergic responses and reproductive physiology.

Date: 1997
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DOI: 10.1038/37622

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