Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito
Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito
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DOI：
10.1182/blood-2007-06-097824
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发表时间：
2008-02-15
期刊：
影响因子：
20.3
通讯作者：
Matsuoka, Hiroyuki
中科院分区：
文献类型：
--
作者：
Yoshida, Shigeto;Sudo, Toshiki;Matsuoka, Hiroyuki
在吸血过程中，蚊子注射含有分子混合物的唾液，这些分子可以灭活或抑制咬伤止血反应的各种成分以及咬伤产生的炎症反应，以促进血液的摄入。然而，单个唾液成分的分子功能在很大程度上仍然未知。本文报道了从人类疟疾媒介按蚊（Anopheles stephensi）唾液中分离到的抗血小板按蚊蛋白（AAPP）。AAPP对胶原诱导的血小板聚集表现出较强的特异性抑制活性。其抑制机制涉及AAPP与胶原的直接结合，阻断血小板与胶原的粘附，抑制随后细胞内Ca2+浓度的增加（[Ca2+]i）。AAPP与胶原蛋白的结合可通过糖蛋白VI （GPVI）和整合素α (2) β(1)有效阻断血小板粘附。细胞粘附实验显示，AAPP抑制了GPVI与I型和III型胶原的结合，对GPVI无直接影响。此外，静脉给药重组AAPP强烈抑制胶原诱导的大鼠体外血小板聚集。综上所述，AAPP是一种疟疾媒介蚊子衍生的特异性受体拮抗剂，可介导血小板与胶原蛋白的粘附。我们的研究可能为阐明蚊子吸血对宿主止血的作用提供重要的见解。
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 alpha(2)beta(1). 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.