Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro
Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro
复制标题
DOI：
10.1161/atvbaha.107.152058
复制
发表时间：
2008-02-01
影响因子：
8.7
通讯作者：
Cox, Dermot
中科院分区：
文献类型：
--
作者：
Kerrigan, Steven W.;Clarke, Niamh;Cox, Dermot
目的：金黄色葡萄球菌是感染性心内膜炎（IE）最常见的病原菌，其特征是在心脏瓣膜上形成血栓，并可栓塞到远处部位。之前，我们发现金黄色葡萄球菌聚集因子A （ClfA）和纤维连接蛋白结合蛋白A （FnBPA）可以刺激血小板快速聚集。方法与结果：在本研究中，我们研究了它们在生理剪切条件下介导聚集体形成中的相关作用。血小板在剪切速率< 500 S（-1）时不能与固定的野生型金黄色葡萄球菌（Newman）相互作用，但在剪切速率为bb0 800 S（-1）时迅速形成聚集体。ClfA基因的失活消除了任何剪切速率下聚集体的形成。使用不与血小板相互作用的替代宿主，过表达ClfA的细菌支持高剪切下的快速聚集形成，与Newman相似，而过表达FnBPA的细菌则没有。纤维蛋白原与ClfA的结合被发现是聚集形成的必要条件，尽管纤维蛋白原包覆的表面只允许单个血小板在所有剪切条件下粘附。阻断血小板免疫球蛋白受体Fc γ RIIa可抑制聚集体的形成。因此，纤维蛋白原和IgG与ClfA的结合对于动脉剪切条件下的聚集形成至关重要，这可能解释了为什么金黄色葡萄球菌是IE的主要原因。
Objective-Staphylococcus aureus is the most frequent causative organism of infective endocarditis (IE) and is characterized by thrombus formation on a cardiac valve that can embolize to a distant site. Previously, we showed that S aureus clumping factor A (ClfA) and fibronectin-binding protein A ( FnBPA) can stimulate rapid platelet aggregation.Methods and Results-In this study we investigate their relative roles in mediating aggregate formation under physiological shear conditions. Platelets failed to interact with immobilized wild-type S aureus (Newman) at shear rates < 500 s(-1) but rapidly formed an aggregate at shear rates > 800 s(-1). Inactivation of the ClfA gene eliminated aggregate formation at any shear rate. Using surrogate hosts that do not interact with platelets bacteria overexpressing ClfA supported rapid aggregate formation under high shear with a similar profile to Newman whereas bacteria overexpressing FnBPA did not. Fibrinogen binding to ClfA was found to be essential for aggregate formation although fibrinogen-coated surfaces only allowed single-platelets to adhere under all shear conditions. Blockade of the platelet immunoglobulin receptor Fc gamma RIIa inhibited aggregate formation.Conclusions-Thus, fibrinogen and IgG binding to ClfA is essential for aggregate formation under arterial shear conditions and may explain why S aureus is the major cause of IE.