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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2007-2014. Prepublished online as a Blood First Edition Paper on December 4, 2007; DOI 10.1182/blood-2007-06-097824. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-06-097824v1 111/4/2007    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Yoshida, S. Articles by Matsuoka, H. PubMed PubMed Citation Articles by Yoshida, S. Articles by Matsuoka, H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito Shigeto Yoshida1, Toshiki Sudo2, Masashi Niimi3, Lian Tao3, Bing Sun3, Junichi Kambayashi3, Hiroyuki Watanabe1, Enjie Luo1, and Hiroyuki Matsuoka1 1 Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi, Japan; 2 First Institute of New Drug Discovery, Otsuka Pharmaceutical, Tokushima, Japan; and 3 Otsuka Maryland Medicinal Laboratories, Rockville, MD During blood feeding, mosquitoes inject saliva containing a mixture of molecules that inactivate or inhibit various components of the hemostatic response to the bite injury as well as the inflammatory reactions produced by the bite, to facilitate the ingestion of blood. However, the molecular functions of the individual saliva components remain largely unknown. Here, we describe anopheline antiplatelet protein (AAPP) isolated from the saliva of Anopheles stephensi, a human malaria vector mosquito. AAPP exhibited a strong and specific inhibitory activity toward collagen-induced platelet aggregation. The inhibitory mechanism involves direct binding of AAPP to collagen, which blocks platelet adhesion to collagen and inhibits the subsequent increase in intracellular Ca2+ concentration ([Ca2+]i). The binding of AAPP to collagen effectively blocked platelet adhesion via glycoprotein VI (GPVI) and integrin 2β1. Cell adhesion assay showed that AAPP inhibited the binding of GPVI to collagen type I and III without direct effect on GPVI. Moreover, intravenously administered recombinant AAPP strongly inhibited collagen-induced platelet aggregation ex vivo in rats. In summary, AAPP is a malaria vector mosquito-derived specific antagonist of receptors that mediate the adhesion of platelets to collagen. Our study may provide important insights for elucidating the effects of mosquito blood feeding against host hemostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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