Staphylococcus aureus α-Hemolysin Promotes Platelet-Neutrophil Aggregate Formation
Staphylococcus aureus α-Hemolysin Promotes Platelet-Neutrophil Aggregate Formation
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DOI：
10.1093/infdis/jit235
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发表时间：
2013-09-01
影响因子：
6.4
通讯作者：
Bryant, Amy E.
中科院分区：
文献类型：
--
作者：
Parimon, Tanyalak;Li, Zhi;Bryant, Amy E.
社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）引起严重的出血坏死性肺炎，死亡率高。外毒素已被牵连在这种感染的发病机制;然而，负责的细胞机制仍然在很大程度上不明确。由于血小板-中性粒细胞聚集体（PNAs）可以失调炎症反应并导致组织破坏，我们研究了MRSA的外毒素是否可以刺激人全血中PNAs的形成。强PNA形成刺激毒素从稳定期，但不是对数期CA-MRSA，和α-溶血素被单独确定为这种活动的介质。MRSA外毒素还引起中性粒细胞（多形核白细胞）活化，如通过增加CD 11b表达所测量的，尽管血小板结合不是由该机制驱动的;相反，α-溶血素诱导的PNA形成仅依赖于血小板P-选择素。这些发现表明S.金黄色葡萄球菌α-溶血素诱导的PNA形成在由CA-MRSA引起的出血性/坏死性肺炎中的肺泡毛细血管破坏中，并提供了新的干预靶点。
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe hemorrhagic necrotizing pneumonia associated with high mortality. Exotoxins have been implicated in the pathogenesis of this infection; however, the cellular mechanisms responsible remain largely undefined. Because platelet-neutrophil aggregates (PNAs) can dysregulate inflammatory responses and contribute to tissue destruction, we investigated whether exotoxins from MRSA could stimulate formation of PNAs in human whole blood. Strong PNA formation was stimulated by toxins from stationary phase but not log phase CA-MRSA, and alpha-hemolysin was singularly identified as the mediator of this activity. MRSA exotoxins also caused neutrophil (polymorphonuclear leukocyte) activation, as measured by increased CD11b expression, although platelet binding was not driven by this mechanism; rather, alpha-hemolysin-induced PNA formation was solely platelet P-selectin dependent. These findings suggest a role for S. aureus alpha-hemolysin-induced PNA formation in alveolar capillary destruction in hemorrhagic/necrotizing pneumonia caused by CA-MRSA and offer novel targets for intervention.