Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction

被引：93

作者：

Marcos, Veronica ^{[1
]}

Zhou-Suckow, Zhe ^{[2
]}

Yildirim, Ali Oender ^{[3
,4
]}

Bohla, Alexander ^{[3
,4
]}

Hector, Andreas ^{[1
,5
,6
]}

Vitkov, Ljubomir ^{[7
,8
]}

Krautgartner, Wolf Dietrich ^{[8
]}

Stoiber, Walter ^{[8
]}

Griese, Matthias ^{[1
]}

Eickelberg, Oliver ^{[3
,4
]}

Mall, Marcus A. ^{[2
]}

Hartl, Dominik ^{[1
,5
,6
]}

机构：

[1] Univ Munich, German Ctr Lung Res DZL, Hauner Childrens Hosp, Dept Pediat Pulmonol, D-80377 Munich, Germany

[2] Heidelberg Univ, German Ctr Lung Res DZL, Translat Lung Res Ctr Heidelberg TLRC, Dept Translat Pulmonol, D-69120 Heidelberg, Germany

[3] Univ Munich, Univ Hosp, Inst Lung Biol & Dis iLBD, Comprehens Pneumol Ctr, D-81377 Munich, Germany

[4] German Ctr Lung Res DZL, Helmholtz Zentrum Munchen, D-81377 Munich, Germany

[5] Univ Tubingen, Childrens Hosp, D-72076 Tubingen, Germany

[6] Univ Tubingen, Interdisciplinary Ctr Infect Dis, D-72076 Tubingen, Germany

[7] Univ Saarland, Dept Operat Dent & Periodontol, D-66424 Homburg, Germany

[8] Salzburg Univ, Dept Cell Biol, Div Anim Struct & Funct, Biomed Ultrastruct Res Lab, A-5020 Salzburg, Austria

来源：

MEDIATORS OF INFLAMMATION | 2015年 / 2015卷

关键词：

NEUTROPHIL EXTRACELLULAR TRAPS; SURFACTANT-PROTEIN-D; MOLECULAR-MECHANISMS; INFLAMMATORY MARKERS; MITOCHONDRIAL-DNA; LUNG-DISEASE; RELEASE; SPUTUM; ELASTASE; NETOSIS;

D O I：

10.1155/2015/408935

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：11

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