Erythromycin suppresses neutrophil extracellular traps in smoking-related chronic pulmonary inflammation

Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we exp...

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Bibliographic Details
Published in:Cell death & disease 2019-09, Vol.10 (9), p.678-15, Article 678
Main Authors: Zhang, Hui, Qiu, Shi-Lin, Tang, Qi-Ya, Zhou, Xiu, Zhang, Jian-Quan, He, Zhi-Yi, Bai, Jing, Li, Mei-Hua, Deng, Jing-Min, Liang, Yi, Zhong, Xiao-Ning
Format: Article
Language:English
Subjects:
Adaptive immunity
Animals
Antibiotics
B7-2 Antigen - metabolism
CD40 antigen
CD40 Antigens - metabolism
CD86 antigen
Chronic obstructive pulmonary disease
Cigarette smoke
Cigarette Smoking - adverse effects
Cigarettes
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - metabolism
Emphysema
Erythromycin
Erythromycin - pharmacology
Erythromycin - therapeutic use
Extracellular Traps - drug effects
Fluorescent Antibody Technique
Helper cells
Humans
Inflammation
Inflammation - drug therapy
Inflammation - etiology
Lung diseases
Lymphocytes T
Male
Mice
Mice, Inbred C57BL
Monocytes
Neutrophils
Neutrophils - drug effects
Neutrophils - metabolism
Obstructive lung disease
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - etiology
Respiratory tract
Respiratory tract diseases
Smoking
Sputum
Th1 Cells - drug effects
Th1 Cells - metabolism
Th17 Cells - drug effects
Th17 Cells - metabolism
Tobacco smoke
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Summary:Neutrophil extracellular traps (NETs) may play a critical role in smoking-related chronic airway inflammation. However, the mechanism by which NETs induced by cigarette smoke initiate the adaptive immunity in chronic obstructive pulmonary disease (COPD) is not fully understood. In this study, we explored the effects of NETs induced by cigarette smoke on the myeloid dendritic cells (mDCs) and Th1 and Th17 cells. Additionally, we observed the inhibitory effect of erythromycin on NETs induced by cigarette smoke. We found that elevated NET levels in the sputum of COPD patients were correlated with the circulating Th1 response, mDC activation and airflow limitation. NETs induced by cigarette smoke extract (CSE) could activate monocyte-derived mDCs and promote Th1 and Th17 differentiation in vitro. Erythromycin effectively inhibited NET formation induced by CSE. In vivo, erythromycin decreased NETs in the airway and ameliorated emphysema with Th1 and Th17 cell down-regulation and CD40 and CD86 mDCs suppression in mice chronically exposed to cigarette smoke. These findings provide direct evidence that NETs promote the differentiation of Th1 and Th17 and play a role in the adaptive immunity of smoking-related chronic lung inflammation. Erythromycin is a potential therapeutic strategy for NETs inhibition in COPD.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-019-1909-2