Hawiger J, Steckley S, Hammond D, Cheng C, Timmons S, Glick A D, Des Prez R M
J Clin Invest. 1979 Oct;64(4):931-7. doi: 10.1172/JCI109559.
Bloodstream infections with staphylococci are accompanied by thromboembolic complications. We have studied the mechanism of the interaction of staphylococci with human blood platelets. Staphylococci that possess protein A, a bacterial receptor for the Fc fragment of immunoglobulin G (IgG), caused aggregation of human platelets in whole plasma accompanied by release of [(3)H]serotonin. These reactions were time and concentration dependent, requiring two or more staphylococci per platelet to give maximal response within 5 min. The interaction between staphylococci and platelets required the presence of cell wall-bound protein A and of IgG with an intact Fc fragment. It did not require an intact complement system. Cell wall-bound protein A (solid phase) was capable of aggregating human platelets in whole plasma. In contrast, free, solubilized protein A (fluid phase) did not cause measurable aggregation, and release of [(3)H]serotonin was reduced. An excess of free, solubilized protein A blocked aggregation of human platelets induced by staphylococci in whole plasma. The role of the Fc fragment of IgG in the staphylococci-human platelet interaction was demonstrated by an experiment in which free, isolated Fc fragment blocked aggregation of platelets in whole plasma induced by staphylococci. Furthermore, binding of (125)I-protein A to human platelets was demonstrated in the presence of complete IgG with intact Fc fragment but not in the presence of the F(ab)(2) fragment. Binding of the protein A-IgG complex to the human platelet Fc receptor was paralleled by the release of [(3)H]serotonin. These results represent a novel example of the interaction of two phylogenetically different Fc receptors, one on prokaryotic staphylococci and the other on human platelets. Their common ligand, IgG, is amplified by one Fc receptor (protein A) to react with another Fc receptor present on human platelets, which results in membrane-mediated aggregation and release reaction occurring in whole plasma. This mechanism can be of significance in the pathomechanism of thromboembolic complications at the site(s) of intravascular staphylococcal infection.
葡萄球菌引起的血流感染伴有血栓栓塞并发症。我们研究了葡萄球菌与人血小板相互作用的机制。具有蛋白A（免疫球蛋白G（IgG）Fc片段的细菌受体）的葡萄球菌可导致全血中人类血小板聚集，并伴有[³H]5-羟色胺的释放。这些反应具有时间和浓度依赖性，每个血小板需要两个或更多葡萄球菌才能在5分钟内产生最大反应。葡萄球菌与血小板之间的相互作用需要细胞壁结合的蛋白A和具有完整Fc片段的IgG的存在。它不需要完整的补体系统。细胞壁结合的蛋白A（固相）能够使全血中的人类血小板聚集。相比之下，游离的、可溶的蛋白A（液相）不会引起可测量的聚集，并且[³H]5-羟色胺的释放减少。过量的游离、可溶蛋白A可阻断葡萄球菌在全血中诱导的人类血小板聚集。通过一项实验证明了IgG的Fc片段在葡萄球菌-人类血小板相互作用中的作用，在该实验中，游离的、分离的Fc片段可阻断葡萄球菌在全血中诱导的血小板聚集。此外，在具有完整Fc片段的完整IgG存在下可证明¹²⁵I-蛋白A与人血小板的结合，但在F(ab)₂片段存在下则不能。蛋白A-IgG复合物与人血小板Fc受体的结合与[³H]5-羟色胺的释放平行。这些结果代表了两种系统发育不同的Fc受体相互作用的新例子，一种存在于原核葡萄球菌上，另一种存在于人类血小板上。它们的共同配体IgG被一种Fc受体（蛋白A）放大，以与人类血小板上存在的另一种Fc受体反应，这导致在全血中发生膜介导的聚集和释放反应。这种机制在血管内葡萄球菌感染部位的血栓栓塞并发症发病机制中可能具有重要意义。
