The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/6/1779/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 11, June 1, 1998 1779-1788

Articles

Impaired Anaphylactic Responses with Intact Sensitivity to Endotoxin in Mice Lacking a Platelet-activating Factor Receptor

Satoshi Ishii*,¶, Tomoyuki Kuwaki{ddagger}, Takahide Nagase§, Kazushige Maki||, Fumi Tashiro||, Shinji Sunaga||, Wei-Hua Cao{ddagger}, Kazuhiko Kume*, Yoshinosuke Fukuchi§, Koichi Ikuta||, Jun-ichi Miyazaki||, Mamoru Kumada{ddagger}, and Takao Shimizu*

From the * Department of Biochemistry and Molecular Biology, the {ddagger} Department of Physiology, the § Department of Geriatrics, and the || Department of Disease-related Gene Regulation Research (Sandoz), Faculty of Medicine, The University of Tokyo, Tokyo 113, Japan; and the Pharmaceutical Basic Research Laboratories (Aobadai), Japan Tobacco Inc., Kanagawa 227, Japan

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor–deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.

Key Words: platelet-activating factor • platelet-activating factor receptor • anaphylaxis • endotoxic shock • gene targeting

Address correspondence to Takao Shimizu, Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113, Japan. Phone: 81-3-5802-2925; Fax: 81-3-3813-8732; E-mail: tshimizu{at}m.u-tokyo.ac.jp

Abbreviations used: ANOVA, analysis of variance; ES, embryonic stem; HR, heart rate; LTB4, leukotriene B4; MAP, mean arterial pressure; NO, nitric oxide; PAF, platelet-activating factor; RL, total lung resistance.


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