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, 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.
Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, Germany.
Veronica
V
Marcos
Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), University of Heidelberg, The German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
Zhe
Z
Zhou-Suckow
Comprehensive 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, Germany.
Ali
A
Önder Yildirim
Comprehensive 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, Germany.
Alexander
A
Bohla
Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, Germany ; Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen, 72076 Tübingen, Germany.
Andreas
A
Hector
Department of Operative Dentistry & Periodontology, Saarland University, 66424 Homburg, Germany ; Biomedical Ultrastructure Research Lab, Division of Animal Structure and Function, Department of Cell Biology, University of Salzburg, 5020 Salzburg, Austria.
Ljubomir
L
Vitkov
Biomedical Ultrastructure Research Lab, Division of Animal Structure and Function, Department of Cell Biology, University of Salzburg, 5020 Salzburg, Austria.
Wolf Dietrich
WD
Krautgartner
Biomedical Ultrastructure Research Lab, Division of Animal Structure and Function, Department of Cell Biology, University of Salzburg, 5020 Salzburg, Austria.
Walter
W
Stoiber
Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, Germany.
Matthias
M
Griese
Comprehensive 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, Germany.
Oliver
O
Eickelberg
Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), University of Heidelberg, The German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
Marcus A
MA
Mall
Department of Pediatric Pulmonology, Hauner Children's Hospital, Ludwig Maximilians University, The German Center for Lung Research (DZL), 80377 Munich, Germany ; Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen, 72076 Tübingen, Germany.
Dominik
D
Hartl
D000293:Adolescent; D000328:Adult; D000402:Airway Obstruction / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019743:Chemokines, CXC / Q000378:metabolism; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology*; D008024:Ligands; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D055815:Young Adult
D019743:Chemokines, CXC; D008024:Ligands; D004247:DNA