Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease.
Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease.
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DOI：
10.1016/j.jaci.2017.04.022
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Chalmers JD
中科院分区：
文献类型：
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作者：
Dicker AJ;Crichton ML;Pumphrey EG;Cassidy AJ;Suarez-Cuartin G;Sibila O;Furrie E;Fong CJ;Ibrahim W;Brady G;Einarsson GG;Elborn JS;Schembri S;Marshall SE;Palmer CNA;Chalmers JD
中性粒细胞胞外陷阱（NETs）已在慢性阻塞性肺疾病（COPD）患者的气道中观察到，但其临床和病理生理意义尚未明确。我们试图确定NETs是否与COPD患者的疾病严重程度相关，以及它们如何与微生物群组成和气道中性粒细胞功能相关。对COPD患者在疾病稳定期和加重期的可溶性痰液和血清中的净蛋白复合物（DNA-弹性酶和组蛋白-弹性酶复合物）、无细胞DNA和中性粒细胞生物标志物进行量化，并与疾病严重程度和痰微生物组的临床指标进行比较。体外及实验观察NET刺激后外周血及气道中性粒细胞功能的变化。痰NET复合物与COPD严重程度相关，采用全球阻塞性肺疾病倡议（Global Initiative for Obstructive Lung Disease）综合量表进行评估（P < 0.0001）。这种关系是由于NET复合物与FEV1、使用COPD评估试验评估的症状以及频繁加重患者较高水平的NET复合物之间存在适度相关性（P = 0.002）。微生物群组成具有异质性，但净复合体与微生物群多样性（P = 0.009）和嗜血杆菌种类操作分类单位优势度（P = 0.01）均存在相关性。痰中NET复合物增加的患者体外气道中性粒细胞吞噬能力降低。无论采用何种方法定量痰NETs，结果均一致。慢性阻塞性肺病患者可溶性痰液与健康对照中性粒细胞孵育可诱导吞噬失败。NET的形成在严重COPD患者中增加，并与更频繁的恶化和微生物群多样性的丧失有关。
Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined. We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. NET protein complexes (DNA-elastase and histone-elastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.
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影响因子：
2.5
作者：
Greenwood H;Patel J;Mahida R;Wang Q;Parekh D;Dancer RC;Khiroya H;Sapey E;Thickett DR
通讯作者：
Thickett DR
影响因子：
27.4
作者：
Knight JS;Subramanian V;O'Dell AA;Yalavarthi S;Zhao W;Smith CK;Hodgin JB;Thompson PR;Kaplan MJ
通讯作者：
Kaplan MJ
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
DOI：
10.1164/rccm.201210-1913oc
发表时间：
2013-05-15
影响因子：
24.7
作者：
Morris, Alison;Beck, James M.;Weinstock, George M.
通讯作者：
Weinstock, George M.
影响因子：
82.9
作者：
通讯作者：
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