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Role of cytosolic phospholipase A2 in allergic response and parturition

Nature volume 390, pages 618–622 (1997)Cite this article

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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Figure 1: Disruption of the cPLA2 gene in mice.
Figure 2: Disruption of the cPLA2 gene in mice.
Figure 3: Disruption of the cPLA2 gene in mice.
Figure 4: Disruption of the cPLA2 gene in mice.
Figure 5: Production of eicosanoids and PAF in peritoneal macrophages.
Figure 6: Production of eicosanoids and PAF in peritoneal macrophages.
Figure 7: Production of eicosanoids and PAF in peritoneal macrophages.
Figure 8: Allergic responses in the bronchopulmonary system.
Figure 9: Allergic responses in the bronchopulmonary system.
Figure 10: Allergic responses in the bronchopulmonary system.

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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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Author notes

  1. Fumi Tashiro & Jun-ichi Miyazaki

    Present address: Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Yamada-oka 2-2, Suita, Osaka, 565, Japan

  2. Kazushige Maki & Koichi Ikuta

    Present address: Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606, Japan

Authors and Affiliations

  1. Departments of Biochemistry and Molecular Biology, Geriatrics, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Naonori Uozumi, Kazuhiko Kume, Noriaki Nakatani, Satoshi Ishii & Takao Shimizu

  2. Departments of Geriatrics, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Takahide Nagase & Yasuyoshi Ouchi

  3. Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1 Aoba-ku, Sendai, 980-77, Miyagi, Japan

    Fumi Tashiro, Yoshinori Komagata & Jun-ichi Miyazaki

  4. Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113, Tokyo, Japan

    Kazushige Maki & Koichi Ikuta

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Correspondence to Takao Shimizu.

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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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