Characterization of well-differentiated bronchial epithelial cells derived from severe COPD patients

Airway epithelium plays a pivotal role in maintaining immune homeostasis and orchestrates the innate and adaptive responses of the lung against inhaled insults. However, the aetiology of pathological changes on airway epithelium during COPD pathogenesis is not completely understood, in particular factors linked to the susceptibility to severe disease. To address this, we characterized well-differentiated primary bronchial epithelial cells (WD-PBECs) derived from severe COPD patients undergoing transplantation and age-matched healthy controls employing an air-liquid interface (ALI) 3D in vitro/ex-vivo culture model. WD-PBECs derived from severe COPD patients showed an indistinguishable morphology compared with controls. However, aberrant epithelium differentiation in terms of a decrease in the number of ciliated cells and an increase in the number of Club cells and goblet cells in was evidenced in COPD cultures compared with healthy controls. Tight junction integrity was also compromised in the former. Moreover, there was enhanced basolateral secretion of IL-6, IL-8, GM-CSF, IL-1alpha, IP-10, CCL1 as well as altered secretion of Th1 and Th2 cytokines by COPD cells. Our data demonstrate that primary bronchial epithelial cells from patients with severe COPD show alterations in individual cell types during differentiation and enhanced secretion of inflammatory mediators including an alteration in Th1 and Th2 cytokines. Such changes in COPD bronchial epithelium during severe disease may represent an underlying perturbation in cellular function in these cells which may contribute to inflammation and infection in the COPD airways.