Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy.
Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy.
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DOI：
10.3389/fimmu.2021.757041
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发表时间：
2021
影响因子：
7.3
通讯作者：
Cui N
中科院分区：
文献类型：
--
作者：
Mao JY;Zhang JH;Cheng W;Chen JW;Cui N
中性粒细胞胞外陷阱(Net)是炎症和凝血的重要触发因子。我们假设Net与败血症的高凝状态有关。共纳入2017年2月至2018年4月北京协和医院重症监护内科收治的败血症患者82例。记录临床和血液学参数以及血栓或出血事件。采集血液样本以评估网络形成的生物标志物，包括中性粒细胞弹性蛋白酶2(ELA2)和瓜氨酸组蛋白H3，以及内皮衍生生物标志物Syndecan-1。我们还检测了自噬水平及其调控途径，以探讨它们与NETs的相互作用。有弥散性血管内凝血的脓毒症患者的净形成水平显著高于对照组[ELA2，1,247(86-625)vs 2,039(1,544-2,534)，p<；0.0001；H3140(47-233)vs.307(199-415)，p<；0.0001]。净形成与DIC风险[ELA2，OR 1.0028，95%CI，1.0010-1.0045；H3，OR 1.0104，95%CI，1.0032-1.0176]和死亡率[ELA2，HR 1.0014，95%CI，1.0004-1.0024；H3，HR 1.0056，95%CI，1.0008-1.0115]独立相关。ELA2预测DIC的曲线下面积为0.902(95%CI，0.816~0.957)，H3预测DIC的曲线下面积为0.870(95%CI，0.778~0.934)。此外，网络形成、内皮细胞和自噬的生物标志物显示出显著的相关性[Ela2与Syn(r=0.5985，p<；0.0001)，Lc3b(r=−0.4224，p<；0.0001)；H3与Syn(r=0.6383，p<；0.0001)，Lc3b(r=−0.3005，p=0.0061)]。在脓毒症患者中，净形成的增加与脓毒症引起的DIC的发生率和死亡率显著相关，这揭示了与自噬途径的显著关系。Chictr.org.cn，识别符ChiCTR-ROC-17010750。
Neutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability. In total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Clinical and hematological parameters and thrombotic or hemorrhagic events were recorded. Blood samples were obtained to assess biomarkers of NET formation, including neutrophil elastase 2 (ELA2) and citrullinated histone H3, and endothelial-derived biomarker syndecan-1. Autophagy levels and their regulation pathway were also examined to explore their interaction with NETs. Sepsis patients with disseminated intravascular coagulation (DIC) showed significantly higher levels of NET formation [ELA2, 1,247 (86–625) vs. 2,039 (1,544–2,534), p < 0.0001; H3, 140 (47–233) vs. 307 (199–415), p < 0.0001]. NET formation was independently associated with DIC risk [ELA2, OR 1.0028, 95% CI, 1.0010–1.0045; H3, OR 1.0104, 95% CI, 1.0032–1.0176] and mortality [ELA2, HR 1.0014, 95% CI, 1.0004–1.0024; H3, HR 1.0056, 95% CI, 1.0008–1.0115]. The area under the curve value for ELA2 in predicting DIC occurrence was 0.902 (95% CI, 0.816–0.957), and that of H3 was 0.870 (95% CI, 0.778–0.934). Furthermore, biomarkers of NET formation, endothelial cells, and autophagy exhibited a significant correlation [ELA2 and Syn (r = 0.5985, p < 0.0001), LC3B (r = −0.4224, p < 0.0001); H3 and Syn (r = 0.6383, p < 0.0001), LC3B (r = −0.3005, p = 0.0061)]. Increased NET formation is significantly associated with sepsis-induced DIC incidence and mortality in sepsis patients, revealing a significant relationship with the autophagy pathway. chictr.org.cn, identifier ChiCTR-ROC-17010750.