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: 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, Dominik Hartl
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/408935
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author 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
Dominik Hartl
author_facet 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
Dominik Hartl
author_sort Veronica Marcos
collection DOAJ
description 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.
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institution Kabale University
issn 0962-9351
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language English
publishDate 2015-01-01
publisher Wiley
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series Mediators of Inflammation
spelling doaj-art-7f20556708274fb79a6bada68829051d2025-02-03T06:42:05ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/408935408935Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow ObstructionVeronica Marcos0Zhe Zhou-Suckow1Ali Önder Yildirim2Alexander Bohla3Andreas Hector4Ljubomir Vitkov5Wolf Dietrich Krautgartner6Walter Stoiber7Matthias Griese8Oliver Eickelberg9Marcus A. Mall10Dominik Hartl11Department of Pediatric Pulmonology, Hauner Children’s Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, GermanyDepartment of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), University of Heidelberg, The German Center for Lung Research (DZL), 69120 Heidelberg, GermanyComprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), University Hospital, Ludwig Maximilians University and Helmholtz Zentrum München, The German Center for Lung Research (DZL), 81377 Munich, GermanyComprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), University Hospital, Ludwig Maximilians University and Helmholtz Zentrum München, The German Center for Lung Research (DZL), 81377 Munich, GermanyDepartment of Pediatric Pulmonology, Hauner Children’s Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, GermanyDepartment of Operative Dentistry & Periodontology, Saarland University, 66424 Homburg, GermanyBiomedical Ultrastructure Research Lab, Division of Animal Structure and Function, Department of Cell Biology, University of Salzburg, 5020 Salzburg, AustriaBiomedical Ultrastructure Research Lab, Division of Animal Structure and Function, Department of Cell Biology, University of Salzburg, 5020 Salzburg, AustriaDepartment of Pediatric Pulmonology, Hauner Children’s Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, GermanyComprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), University Hospital, Ludwig Maximilians University and Helmholtz Zentrum München, The German Center for Lung Research (DZL), 81377 Munich, GermanyDepartment of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), University of Heidelberg, The German Center for Lung Research (DZL), 69120 Heidelberg, GermanyDepartment of Pediatric Pulmonology, Hauner Children’s Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, GermanyChronic 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.http://dx.doi.org/10.1155/2015/408935
spellingShingle 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
Dominik Hartl
Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
Mediators of Inflammation
title Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
title_full Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
title_fullStr Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
title_full_unstemmed Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
title_short Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction
title_sort free dna in cystic fibrosis airway fluids correlates with airflow obstruction
url http://dx.doi.org/10.1155/2015/408935
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