Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease

作者：Alison Dicker, Megan Louise Crichton, Eleanor Pumphrey, Andrew J. CASSIDY, Guillermo Suárez-Cuartín, Oriol Sibila, Elizabeth Furrie, Christopher John Fong, Wasyla Ibrahim, Gill Brady, Gisli G. Einarsson, J.S. Elborn, Stuart Schembri, Sara E. Marshall, Colin N.A. Palmer, James Duncan Chalmers · 发表于：Journal of Allergy and Clinical Immunology · 年份：2017 · DOI：10.1016/j.jaci.2017.04.022 · 被引用次数：301 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Immune cells in cancer、Chronic Obstructive Pulmonary Disease (COPD) Research

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: , 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 ...