J. Exp. Med., Volume 187, Number 11, June 1, 1998 1779-1788

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

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

From the ^* Department of Biochemistry and Molecular Biology, the  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.

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