Neutrophil Extracellular Traps Are Pathogenic in Ventilator-Induced Lung Injury and Partially Dependent on TLR4.

Neutrophil Extracellular Traps Are Pathogenic in Ventilator-Induced Lung Injury and Partially Dependent on TLR4.
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中性粒细胞胞外陷阱在呼吸机引起的肺损伤中具有致病性,并且部分依赖于 TLR4

DOI:
10.1155/2017/8272504
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发表时间:
2017
影响因子:
--
通讯作者:
Chen J
Chen J
中科院分区:
生物学3区
文献类型:
--
作者:
Li H;Pan P;Su X;Liu S;Zhang L;Wu D;Li H;Dai M;Li Y;Hu C;Chen J

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呼吸机诱导肺损伤(VILI)的发病机制与中性粒细胞有关。中性粒细胞释放由DNA和颗粒蛋白组成的中性粒细胞胞外陷阱(NETs)。然而,在VILI中,net的作用仍然没有被完全理解。用生理盐水和脱氧核糖核酸酶(DNase)研究NETs在VILI中的作用。为了进一步确定toll样受体4 (TLR4)在NETosis中的作用,我们评估了TLR4敲除小鼠和机械通气野生型小鼠的肺损伤和NET形成。VILI组肺损伤的一些指标和NETs标志物显著升高。DNase治疗显著降低NETs标记物和肺损伤。高潮汐机械通气后,TLR4 KO小鼠的NETs标记物明显低于WT小鼠。这些数据表明,NETs在VILI中产生,并在VILI小鼠模型中具有致病性,其形成部分依赖于TLR4。
The pathogenesis of ventilator-induced lung injury (VILI) is associated with neutrophils. Neutrophils release neutrophil extracellular traps (NETs), which are composed of DNA and granular proteins. However, the role of NETs in VILI remains incompletely understood. Normal saline and deoxyribonuclease (DNase) were used to study the role of NETs in VILI. To further determine the role of Toll-like receptor 4 (TLR4) in NETosis, we evaluated the lung injury and NET formation in TLR4 knockout mice and wild-type mice that were mechanically ventilated. Some measures of lung injury and the NETs markers were significantly increased in the VILI group. DNase treatment markedly reduced NETs markers and lung injury. After high-tidal mechanical ventilation, the NETs markers in the TLR4 KO mice were significantly lower than in the WT mice. These data suggest that NETs are generated in VILI and pathogenic in a mouse model of VILI, and their formation is partially dependent on TLR4.
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