Vascular dysfunction and ischemic destruction of tissue in streptococcus pyogenes infection: The role of streptolysin O - Induced platelet/neutrophil complexes
Vascular dysfunction and ischemic destruction of tissue in streptococcus pyogenes infection: The role of streptolysin O - Induced platelet/neutrophil complexes
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DOI：
10.1086/432729
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发表时间：
2005-09-15
影响因子：
6.4
通讯作者：
Stevens, DL
中科院分区：
文献类型：
--
作者：
Bryant, AE;Bayer, CR;Stevens, DL
A组链球菌（GAS）坏死性筋膜炎/肌坏死的快速组织破坏通常需要广泛清创以确保生存。这种暴发性过程的机制尚不清楚，我们假设毒素诱导的缺血导致坏死。在大鼠模型中，使用多普勒血流仪测量肌肉注射来自侵入性M-1型GAS的外毒素的部位的局部血流，这导致灌注的快速、剂量依赖性降低，在测试的最高毒素浓度下是不可逆的。视频显微镜结果显示，血流受阻闭塞血管内细胞聚集。流式细胞术结果证实，GAS毒素诱导血小板和中性粒细胞的共聚集，这种活动是由于链球菌溶血素O，血小板/中性粒细胞复合物的形成主要是由血小板P-选择素（CD 62 P）介导的。靶向血小板粘附分子的策略可以防止血管闭塞，维持组织活力，并减少坏死性GAS感染中截肢的需要。
Rapid tissue destruction in group A streptococcal (GAS) necrotizing fasciitis/myonecrosis often necessitates extensive debridement to ensure survival. The mechanisms responsible for this fulminant process remain unknown; we hypothesized that toxin-induced ischemia contributes to necrosis. In a rat model, Doppler flowmetry was used to measure local blood flow at the site of the intramuscular injection of exotoxins from an invasive M-type 1 GAS, which caused a rapid, dose-dependent decrease in perfusion that was irreversible at the highest toxin concentration tested. Videomicroscopic results revealed that blood flow was impeded by occlusive intravascular cellular aggregates. Flow-cytometric results confirmed that GAS toxins induced the coaggregation of platelets and neutrophils, that this activity was attributable to streptolysin O, and that platelet/neutrophil complex formation was largely mediated by platelet P-selectin (CD62P). Strategies that target platelet adherence molecules may prevent vascular occlusion, maintain tissue viability, and reduce the need for amputation in necrotizing GAS infections.