Abstract
BackgroundCOPD is a progressive disease of the airways that is characterized by neutrophilic inflammation, a condition known to promote the excessive formation of neutrophil extracellular traps (NETs). The presence of large amounts of NETs has recently been demonstrated for a variety of inflammatory lung diseases including cystic fibrosis, asthma and exacerbated COPD.ObjectiveWe test whether excessive NET generation is restricted to exacerbation of COPD or whether it also occurs during stable periods of the disease, and whether NET presence and amount correlates with the severity of airflow limitation.Patients, materials and methodsSputum samples from four study groups were examined: COPD patients during acute exacerbation, patients with stable disease, and smoking and non-smoking controls without airflow limitation. Sputum induction followed the ECLIPSE protocol. Confocal laser microscopy (CLSM) and electron microscopy were used to analyse samples. Immunolabelling and fluorescent DNA staining were applied to trace NETs and related marker proteins. CLSM specimens served for quantitative evaluation.ResultsSputum of COPD patients is clearly characterised by NETs and NET-forming neutrophils. The presence of large amounts of NET is associated with disease severity (p < 0.001): over 90 % in exacerbated COPD, 45 % in stable COPD, and 25 % in smoking controls, but less than 5 % in non-smokers. Quantification of NET-covered areas in sputum preparations confirms these results.ConclusionsNET formation is not confined to exacerbation but also present in stable COPD and correlates with the severity of airflow limitation. We infer that NETs are a major contributor to chronic inflammatory and lung tissue damage in COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a progressive disease of the airways that is characterized by neutrophilic inflammation, a condition known to promote the excessive formation of neutrophil extracellular traps (NETs)
Sputum of COPD patients is clearly characterised by NETs and NET-forming neutrophils
The morphological analyses using Confocal laser microscopy (CLSM), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) show clearly that sputa of both patients with acutely exacerbated COPD and patients with stable COPD are characterised by a massive presence of NETs and neutrophils at various stages of NET formation (Figs. 1 and 2)
Summary
COPD is a progressive disease of the airways that is characterized by neutrophilic inflammation, a condition known to promote the excessive formation of neutrophil extracellular traps (NETs). Grabcanovic-Musija et al Respiratory Research (2015) 16:59 of decondensed chromatin associated with histones and enzymes such as neutrophil elastase (NE) and myeloperoxidase (MPO) that are all both antimicrobial and potentially cytotoxic They are released by activated neutrophils, mainly in a distinct process of cell death termed NETosis [9]. NETs are loaded with strongly alkaline histones and degradative enzymes, and are associated with ROS release and autoantibody induction by citrullinated proteins They have a high cytotoxic potential, and evidence is accumulating that they directly contribute to host cell death and chronic tissue damage when formed in excess or are insufficiently cleared by mechanisms that are still poorly understood [15,16,17,18]. Routine anti-inflammatory treatment with steroids has so far been of limited success in COPD [22], and the presence of neutrophils may be even enhanced under steroid therapy [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
