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首页> 外文期刊>Infection and immunity >Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent mechanism which is independent of principal platelet glycoprotein IIb/IIIa fibrinogen-binding domains.
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Staphylococcus aureus induces platelet aggregation via a fibrinogen-dependent mechanism which is independent of principal platelet glycoprotein IIb/IIIa fibrinogen-binding domains.

机译：金黄色葡萄球菌通过纤维蛋白原依赖性机制诱导血小板聚集，该机制与主要的血小板糖蛋白IIb / IIIa纤维蛋白原结合域无关。

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Platelet aggregation by bacteria is felt to play an important role in the pathogenesis of infective endocarditis. However, the mechanisms involved in bacterium-induced platelet aggregation are not well-defined. In the present study, we examined the mechanisms by which Staphylococcus aureus causes rabbit platelet aggregation in vitro. In normal plasma, the kinetics of S. aureus-induced platelet aggregation were rapid and biphasic. The onset and magnitude of aggregation phase 1 varied with the bacterium-platelet ratio, with maximal aggregation observed at a ratio of 5:1. The onset of aggregation phase 2 was delayed in the presence of apyrase (an ADP hydrolase), suggesting that this later aggregation phase may be triggered by secreted ADP. The onset of aggregation phase 2 was delayed in the presence of prostaglandin I2-treated platelets, and this phase was absent when paraformaldehyde-fixed platelets were used, implicating platelet activation in this process. Platelet aggregation phase 2 was dependent on S. aureus viability and an intact bacterial cell wall, and it was mitigated by antibody directed against staphylococcal clumping factor (a fibrinogen-binding protein) and by the cyclooxygenase inhibitor indomethacin. Similarly, aggregation phase 2 was either delayed or absent in three distinct transposon-induced S. aureus mutants with reduced capacities to bind fibrinogen in vitro. In addition, a synthetic pentadecapeptide, corresponding to the staphylococcal binding domain in the C terminus of the fibrinogen delta-chain, blocked aggregation phase 2. However, phase 2 of aggregation was not inhibited by two synthetic peptides (alone or in combination) analogous to the two principal fibrinogen-binding domains on the platelet glycoprotein (GP) IIb/IIIa integrin receptor: (i) a recognition site on the IIIa molecule for the Arg-Gly-Asp (RGD) sequence of the fibrinogen alpha-chain and (ii) a recognition site on the IIb molecule for a dodecapeptide sequence of the fibrinogen delta-chain. This differs from ADP-induced platelet aggregation, which relies on an intact platelet GP IIb/IIIa receptor with an accessible RGD sequence and dodecapeptide recognition site for fibrinogen. Furthermore, a monoclonal antibody directed against the RGD recognition site on rabbit platelet GP IIb/IIIa receptors failed to inhibit rabbit platelet aggregation by S. aureus. Collectively, these data suggest that S. aureus-induced platelet aggregation requires bacterial binding to fibrinogen but is not principally dependent upon the two major fibrinogen-binding domains on the platelet GP IIb/IIIa integrin receptor, the RGD and dodecapeptide recognition sites.
机译：细菌引起的血小板聚集被认为在感染性心内膜炎的发病机理中起重要作用。然而，涉及细菌诱导的血小板聚集的机制尚不清楚。在本研究中，我们研究了金黄色葡萄球菌在体外引起兔血小板聚集的机制。在正常血浆中，金黄色葡萄球菌诱导的血小板聚集的动力学是快速且双相的。聚集阶段1的发生和大小随细菌-血小板比率的变化而变化，最大聚集比率为5：1。在存在腺苷三磷酸双磷酸酶（ADP水解酶）的情况下，聚集阶段2的发作被延迟，这表明此稍后的聚集阶段可能由分泌的ADP触发。在前列腺素I2处理的血小板存在下，聚集阶段2的发作被延迟，而当使用低聚甲醛固定的血小板时，该阶段不存在，这暗示了该过程中的血小板活化。血小板聚集期2取决于金黄色葡萄球菌的生存能力和完整的细菌细胞壁，并且通过针对葡萄球菌聚集因子（纤维蛋白原结合蛋白）的抗体和环氧合酶抑制剂吲哚美辛来缓解。类似地，在体外转座子结合纤维蛋白原的能力降低的三个不同的转座子诱导的金黄色葡萄球菌突变体中，聚集阶段2被延迟或不存在。另外，对应于纤维蛋白原δ链C末端葡萄球菌结合结构域的合成五肽结合肽阻断了聚集相2。但是，类似于的两个合成肽（单独或组合）并未抑制聚集相2。血小板糖蛋白（GP）IIb / IIIa整联蛋白受体上的两个主要纤维蛋白原结合域：（i）IIIa分子上对纤维蛋白原α链的Arg-Gly-Asp（RGD）序列的识别位点和（ii ）IIb分子上纤维蛋白原δ链十二肽序列的识别位点。这不同于ADP诱导的血小板聚集，后者依赖完整的血小板GP IIb / IIIa受体，该受体具有可及的RGD序列和纤维蛋白原的十二肽识别位点。此外，针对兔血小板GP IIb / IIIa受体上RGD识别位点的单克隆抗体未能抑制金黄色葡萄球菌引起的兔血小板聚集。总体而言，这些数据表明，金黄色葡萄球菌诱导的血小板聚集需要细菌与纤维蛋白原结合，但并不主要依赖于血小板GP IIb / IIIa整合素受体上的两个主要纤维蛋白原结合域，RGD和十二肽识别位点。

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