Research Paper Volume 12, Issue 17 pp 16820—16836
Neutrophil extracellular traps amplify neutrophil recruitment and inflammation in neutrophilic asthma by stimulating the airway epithelial cells to activate the TLR4/ NF-κB pathway and secrete chemokines
- 1 Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- 2 Hunan Provincial Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Changsha, Hunan, China
- 3 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
Received: February 17, 2020 Accepted: May 27, 2020 Published: August 5, 2020
https://doi.org/10.18632/aging.103479How to Cite
Abstract
Neutrophilic asthma (NA) is a distinct airway inflammation disease with prominent neutrophil infiltration. The role played by neutrophil extracellular traps (NETs) in NA, however, is quite unclear. This study was based on the hypothesis that NETs are responsible for the second neutrophil wave and therefore contribute significantly to inflammation. The proinflammatory effects of NETs were evaluated in vitro and in vivo. Formation of NETs and neutrophil swarming was seen in a mouse model of NA. Additionally, NETs were found to stimulate airway cells to express CXCL1, CXCL2, and CXCL8 via the TLR4/NF-κB pathway, which recruits neutrophils to the inflammation site. Furthermore, prevention of NET formation decreased the recruitment of lung neutrophils and hence reduce neutrophilic inflammation. Additionally, the structural integrity of NETs had no effect on the recruitment of lung neutrophils and neutrophilic inflammation. In NA mice, NETs could trigger airway and alveolar epithelial cells to express chemokines which recruit more neutrophils via activation of the TLR4/NF-κB pathway.