Endotoxin transduces Ca2+ signaling via platelet‐activating factor receptor

FEBS Letters

Waga, Iwao¹  Noma, Masana²  Matsumoto, Takashi²  Honda, Zen-ichiro¹  Shimizu, Takao¹  Nakamura, Motonao¹ 

[1] Department of Biochemistry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan;Life Science Research Laboratory, Japan Tobacco Inc., 6-2 Umegaoka, Midori-ku, Yokohama, Kanagawa 227, Japan

关键词: Platelet-activating factor receptor;    Endotoxin;    Lipid A;    Calcium signaling;    Platelet;   

DOI  :  10.1016/0014-5793(92)80957-I

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lipopolysaccharide (LPS) is a pathogenic substance causing severe multiple organ failures and high mortality, Although several LPS binding proteins have been identified, the molecular mechanism underlying the LPS signaling pathway still remains obscure. We have found that the LPS-induced Ca²⁺ increase in platelets and platelet aggregation is blocked by selective platelet-activating factor (PAF) receptor antagonists, thus suggesting a cross-talk between LPS and the PAF receptor. Next, we confirmed this hypothesis using the cloned PAF receptors [(1991) Nature 349, 342–346; (1991) J. Biol. Chem. 266, 20400–20405] expressed in Xenopus occytes and Chinese hamster ovary (CHO) cells. In both systems, cells responded to LPS only when PAF receptors were expressed, and specific PAF binding was successfully displaced and reversibly dissociated by LPS. PAF receptor activation by LPS may represent a novel important pathway in the pathogenesis of circulatory collapse and systemic thrombosis caused by endotoxin.

【 授权许可】

Unknown