Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury.
Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury.
复制标题
中性粒细胞胞外陷阱由脂多糖间接触发并导致急性肺损伤
DOI：
10.1038/srep37252
复制
发表时间：
2016-11-16
影响因子：
4.6
通讯作者：
Tsung A
中科院分区：
文献类型：
--
作者：
Liu S;Su X;Pan P;Zhang L;Hu Y;Tan H;Wu D;Liu B;Li H;Li H;Li Y;Dai M;Li Y;Hu C;Tsung A
神经细胞外陷阱（NET）促进病原体的细胞外杀伤。然而，过多的NET形成和不良的降解与加剧的免疫应答和组织损伤有关。在这项研究中，我们研究了NET在脂多糖（LPS）介导的急性肺损伤（ALI）中的作用，并评估了DNase I在治疗ALI中的应用。此外，我们集中在有争议的问题，是否LPS直接诱导NET在体外释放。在小鼠体内ALI组织中检测到NET形成，并且与增加的NET标记物、瓜氨酸化组蛋白H3组织水平和BALF中的NET-DNA水平相关。DNase I治疗显著降解NET并降低瓜氨酸化组蛋白H3水平，从而保护免受ALI并改善肺水肿和BALF中的总蛋白。此外，DNase I显著降低血浆和BALF中的IL-6和TNF-α水平。在体外，LPS激活的血小板，而不是单独的LPS有效地诱导NET的释放。总之，NET在LPS诱导的ALI过程中形成，引起器官损伤并启动炎症反应。DNase I对NET的降解促进了NET蛋白的清除，并对小鼠的ALI具有保护作用，因此，DNase I可能是一种新的潜在的ALI治疗佐剂。具体而言，LPS通过血小板活化以间接方式诱导NET形成。
Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, excessive NETs formation and poor degradation are associated with exacerbated immune responses and tissue injury. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-mediated acute lung injury (ALI) and assessed the use of DNase I, for the treatment of ALI. Additionally, we focused on the controversial issue of whether LPS directly induces NETs release in vitro. NETs formation was detected in murine ALI tissue in vivo and was associated with increased NETs markers, citrullinated-histone H3 tissue levels and NET-DNA levels in BALF. Treatment with DNase I significantly degraded NETs and reduced citrullinated-histone H3 levels, which protected against ALI and ameliorated pulmonary oedema and total protein in BALF. In addition, DNase I significantly reduced IL-6 and TNF-α levels in plasma and BALF. In vitro, LPS-activated platelets rather than LPS alone efficiently induced NETs release. In conclusion, NETs formed during LPS-induced ALI, caused organ damage and initiated the inflammatory response. NETs degradation by DNase I promoted NET-protein clearance and protected against ALI in mice; thus, DNase I may be a new potential adjuvant for ALI therapy. Specifically, LPS induced NETs formation in an indirect manner via platelets activation.