Free DNA in cystic fibrosis airway fluids correlates with airflow obstruction

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, f...

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Main Authors: Marcos-Nickol, Veronica (Author) , Zhou-Suckow, Zhe (Author) , Önder Yildirim, Ali (Author) , Bohla, Alexander (Author) , Hector, Andreas (Author) , Vitkov, Ljubomir (Author) , Krautgartner, Wolf Dietrich (Author) , Stoiber, Walter (Author) , Griese, Matthias (Author) , Eickelberg, Oliver (Author) , Mall, Marcus A. (Author) , Hartl, Dominik (Author)
Format: Article (Journal)
Language:English
Published: March 31, 2015
In: Mediators of inflammation

ISSN:1466-1861
DOI:10.1155/2015/408935
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1155/2015/408935
Verlag, lizenzpflichtig, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397025/
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Author Notes:Veronica Marcos, Zhe Zhou-Suckow, Ali Önder Yildirim, Alexander Bohla, Andreas Hector, Ljubomir Vitkov, Wolf Dietrich Krautgartner, Walter Stoiber, Matthias Griese, Oliver Eickelberg, Marcus A. Mall, and Dominik Hartl
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Summary: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.
Item Description:Gesehen am 08.06.2020
Physical Description:Online Resource
ISSN:1466-1861
DOI:10.1155/2015/408935