Abstract
Bacterial lipopolysaccharide (LPS) contributes to airway inflammation and mucus hypersecretion in chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Neutrophil extracellular traps (NETs) are extracellular meshworks composed of DNA fibers and antimicrobial proteins. Although NET formation has been detected in COPD and CF patients, how NETs contribute to these diseases is poorly understood. This study was performed to clarify the effects and mechanisms of action of NETs in airway inflammation and mucus hypersecretion. We created a murine model of LPS-induced airway inflammation and mucus hypersecretion, and found that LPS-induced NET formation was degraded by aerosolized DNase I treatment in mice. Degradation of NETs by aerosolized DNase I reduced LPS-induced airway inflammation and mucus hypersecretion in mice, this reduction correlated with suppression of TLR4/NF-κB signaling pathway. More importantly, NETs promoted LPS-induced production of IL-1β, IL-6 and TNF-α in macrophages. These results suggest NET degradation using aerosolized DNase I is a potential new therapeutic strategy for treating COPD and CF.
Highlights
Neutrophil extracellular traps (NETs) are extracellular meshworks composed of decondensed chromatin and characteristic granule proteins, such as histones, myeloperoxidase (MPO), neutrophil elastase (NE) [1]
We created a murine model of LPS-induced airway inflammation and mucus hypersecretion, and found that LPS-induced NET formation was degraded by aerosolized DNase I treatment in mice
NET formation was significantly greater in the LPS group than normal saline (NS) group, which was confirmed by measuring the levels of MPODNA complexes in broncho alveolar lavage fluid (BALF) using a capture enzyme-linked immunosorbent assay (ELISA) kit (Figure 1D)
Summary
Neutrophil extracellular traps (NETs) are extracellular meshworks composed of decondensed chromatin and characteristic granule proteins, such as histones, myeloperoxidase (MPO), neutrophil elastase (NE) [1]. NETosis or NET formation is a distinct and complicated cell death process that differs from apoptosis and necrosis [1, 2]. Citrullination of histone (cit-H3) and heterochromatin decondensation cause NETs formation, and peptidyl arginine deiminase 4 (PAD4) catalyzes this process [3, 4]. With the help of intracellular calcium and MPO, decondensed chromatin and cytosolic protein particles are mixed and NETs formed intracellularly are released to outside of the cell [5]. NETs are cleared by DNase I degradation and macrophages phagocytosis [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
