Abstract
Chronic obstructive lung disease determines morbidity and mortality of patients with cystic fibrosis (CF). CF airways are characterized by a nonresolving neutrophilic inflammation. After pathogen contact or prolonged activation, neutrophils release DNA fibres decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). NETs have been described to act in a beneficial way for innate host defense by bactericidal, fungicidal, and virucidal actions. On the other hand, excessive NET formation has been linked to the pathogenesis of autoinflammatory and autoimmune disease conditions. We quantified free DNA structures characteristic of NETs in airway fluids of CF patients and a mouse model with CF-like lung disease. Free DNA levels correlated with airflow obstruction, fungal colonization, and CXC chemokine levels in CF patients and CF-like mice. When viewed in combination, our results demonstrate that neutrophilic inflammation in CF airways is associated with abundant free DNA characteristic for NETosis, and suggest that free DNA may be implicated in lung function decline in patients with CF.
Highlights
Cystic fibrosis (CF) is a fatal disorder characterized by chronic and progressive lung disease that determines morbidity and mortality of these patients [1]
Most abundant free DNA was found in CF sputa, whereas in bronchoalveolar lavage (BAL) and lung tissue, lower amounts of free DNA strands were detected, which is consistent with the observation that neutrophilic inflammation is most prominent in the proximal/bronchial airway compartments in CF lung disease
A further study found that CF sputum showed NETosis characteristics and implicated macrophage migration-inhibitory factor (MIF) in the formation of neutrophil extracellular traps (NETs) in the context of CF lung disease [12]
Summary
Cystic fibrosis (CF) is a fatal disorder characterized by chronic and progressive lung disease that determines morbidity and mortality of these patients [1]. Airways of CF patients show a chronic nonresolving neutrophilic inflammation, which increases upon infection and disease progression. Neutrophil products, such as elastase, chitinase-like proteins and chemokines, have been identified as important risk factors of lung damage and lung function decline and are suggested as biomarkers based on both cross-sectional and longitudinal studies in patients with CF [2,3,4,5,6,7] and mice with CF-like lung disease [8].
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