Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury
Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury
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DOI：
10.1172/jci61303
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发表时间：
2012-07-01
影响因子：
15.9
通讯作者：
Looney, Mark R.
中科院分区：
文献类型：
--
作者：
Caudrillier, Axelle;Kessenbrock, Kai;Looney, Mark R.
有新的证据表明，血小板是通过与先天免疫细胞密切相关的炎症过程的主要贡献者。在这里，我们报告，活化血小板诱导形成中性粒细胞胞外陷阱（NET）在输血相关的急性肺损伤（TRAM），这是输血治疗后死亡的主要原因。NET由去致密染色质组成，其装饰有颗粒蛋白，其功能是捕获细胞外病原体;它们的形成需要中性粒细胞的活化和在可能导致或可能不导致中性粒细胞死亡的过程中释放其DNA。在嗜中性粒细胞和血小板依赖性TRALI小鼠模型中，NET出现在肺微血管系统中，血浆中NET组分增加。我们检测了人TRALI的肺和血浆以及急性肺损伤患者的血浆中的NET。在实验性TRALI模型中，用阿司匹林或糖蛋白IIb/IIIa抑制剂靶向血小板活化降低了NET形成和肺损伤。然后，我们用组蛋白阻断抗体和DNase 1直接靶向NET组件，这两种抗体都可以保护小鼠免受TRALI的影响。这些数据表明，NET有助于肺内皮损伤，靶向NET形成可能是治疗急性肺损伤的一个有前途的新方向。
There is emerging evidence that platelets are major contributors to inflammatory processes through intimate associations with innate immune cells. Here, we report that activated platelets induce the formation of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRAM), which is the leading cause of death after transfusion therapy. NETs are composed of decondensed chromatin decorated with granular proteins that function to trap extracellular pathogens; their formation requires the activation of neutrophils and release of their DNA in a process that may or may not result in neutrophil death. In a mouse model of TRALI that is neutrophil and platelet dependent, NETs appeared in the lung microvasculature and NET components increased in the plasma. We detected NETs in the lungs and plasma of human TRALI and in the plasma of patients with acute lung injury. In the experimental TRALI model, targeting platelet activation with either aspirin or a glycoprotein IIb/IIIa inhibitor decreased NET formation and lung injury. We then directly targeted NET components with a histone blocking antibody and DNase1, both of which protected mice from TRALI. These data suggest that NETs contribute to lung endothelial injury and that targeting NET formation may be a promising new direction for the treatment of acute lung injury.