The Role Of Neutrophil In Epithelial-mesenchymal Transition In Airway Epithelium Of Patients With COPD

Airway obstruction is the most important pathophysiological changes in COPD, induced to obstructive ventilatory dysfunction. It is closely related to airway remodeling caused by chronic airway inflammation. Neutrophil inflammation predominates in the COPD airway wall and lumen. An extensive body of evidence indicates neutrophil elastase and other nertrophil-derived proteases are key mediators of the tissue damage and relate to the airway remodeling in COPD. Recently, EMT has frequently been mentioned with regard to its involvement in airway remodeling. The transformation of airway epithelial cells via EMT is one of the potential sources for fibrogenic cells within the airway wall. EMT is also likely to be active in the airways of smokers, especially COPD patients who currently smoke. Moreover, it has been demonstrated that neutrophil can induce EMT via elastase in pancreatic and liver tumor cell lines. This observations led us to investigate whether neutrophil is related to EMT occurred in COPD?In order to investigate the role of neutrophils and neutrophil-derived elastase in EMT occured in COPD, the expression of EMT biomarkers and neutrophil infiltration were assessed in lung epithelium specimens; A549cell line was cultured and it was co-cultureed with PMN or NE in vitro. Then small molecular inhibitor of Wnt/β-catenin pathway was used to explor whetherβ-catenin take a part in this process. Markers of active EMT and neutrophil infiltration were significantly increased in the small airway patients with COPD compared with controls. We also observed a significant correlation between neutrophil numbers and vimentin or E-cadherin expression in the airway epithelium. In vitro, PMN-induced EMT in A549cells and it can be inhibited by selective human neutrophil elastase inhibitor Ⅳ. Finally, we demonstrate that the Wnt/β-catenin signaling pathway is required for NE-mediated EMT in A549cells.