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

Abstract

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.

• Authors: Hui Zhang, Shi-Lin Qiu, Qi-Ya Tang, Xiu Zhou, Jian-Quan Zhang, Zhi-Yi He, Jing Bai, Mei-Hua Li, Jing-Min Deng, Yi Liang, Xiao-Ning Zhong
• Journal: Cell death & disease (Cell Death Dis) Vol. 10 Issue 9 Pg. 678 (09 12 2019) ISSN: 2041-4889 [Electronic] England
• PMID: 31515489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-2 Antigen
• CD40 Antigens
• Erythromycin

Topics

• Animals
• B7-2 Antigen (metabolism)
• CD40 Antigens (metabolism)
• Cigarette Smoking (adverse effects)
• Dendritic Cells (drug effects, metabolism)
• Erythromycin (pharmacology, therapeutic use)
• Extracellular Traps (drug effects)
• Fluorescent Antibody Technique
• Humans
• Inflammation (drug therapy, etiology)
• Male
• Mice
• Mice, Inbred C57BL
• Neutrophils (drug effects, metabolism)
• Pulmonary Disease, Chronic Obstructive (drug therapy, etiology)
• Th1 Cells (drug effects, metabolism)
• Th17 Cells (drug effects, metabolism)