Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood
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DOI：
10.1038/nm1565
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发表时间：
2007-04-01
期刊：
影响因子：
82.9
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
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作者：
Clark, Stephen R.;Ma, Adrienne C.;Kubes, Paul
多年来，中性粒细胞和血小板参与严重脓毒症的发病机制，但它们之间的相互关系是完全未知的。我们报道了几个导致细菌在血管中捕获增强的细胞事件：血小板TLR4检测血液中的TLR4配体并诱导血小板与粘附的中性粒细胞结合。这导致稳健的中性粒细胞活化和中性粒细胞胞外陷阱（NETs）的形成。严重脓毒症患者的血浆也会诱导tlr4依赖性血小板-中性粒细胞相互作用，导致NETs的产生。NETs在流动条件下保持其完整性，并在脉管系统中诱捕细菌。整个事件主要发生在肝窦和肺毛细血管中，NETs具有最大的细菌捕获能力。我们提出血小板TLR4是严重脓毒症中这种新的细菌捕获机制的阈值开关。
It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the interrelationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.