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.
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Acknowledgements
We thank I. Kudo for murine cPLA2 cDNA; Y. Hara, Y. Matsumoto, Y. Sakamoto, Y. Suzuki, C. Suzuki, T. Jin and M. Ito for technical assistance; D. W. Saffen for critically reading the manuscript; and S. Narumiya, Y. Taketani, M. Momoeda, T. Izumi, T. Yokomizo, M. Aihara, J. D. Clark and M. Murakami for their valuable suggestions. This work was supported in part by grants-in aid from the Ministry of Education, Science, Sports and Culture of Japan, and by grants form the Human Science Foundation and Senri Life Science Foundation.
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Uozumi, N., Kume, K., Nagase, T. et al. Role of cytosolic phospholipase A2 in allergic response and parturition. Nature 390, 618–622 (1997). https://doi.org/10.1038/37622
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DOI: https://doi.org/10.1038/37622
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