Bronchial epithelial cells: The key effector cells in the pathogenesis of chronic obstructive pulmonary disease?

Abstract

The primary function of the bronchial epithelium is to act as a defensive barrier aiding the maintenance of normal airway function. Bronchial epithelial cells (BECs) form the interface between the external environment and the internal milieu, making it a major target of inhaled insults. However, BECs can also serve as effectors to initiate and orchestrate immune and inflammatory responses by releasing chemokines and cytokines, which recruit and activate inflammatory cells. They also produce excess reactive oxygen species as a result of an oxidant/antioxidant imbalance which contributes to chronic pulmonary inflammation and lung tissue damage. Accumulated mucus from hyperplastic BECs obstructs the lumen of small airways, whereas impaired cell repair, squamous metaplasia and increased extracellular matrix deposition underlying the epithelium is associated with airway remodelling particularly fibrosis and thickening of the airway wall. These alterations in small airway structure lead to airflow limitation, which is critical in the clinical diagnosis of chronic obstructive pulmonary disease (COPD). In this review, we discuss the abnormal function of BECs within a disturbed immune homeostatic environment consisting of ongoing inflammation, oxidative stress and small airway obstruction.We provide an overview of recent insights into the function of the bronchial epithelium in the pathogenesis of COPD and how this may provide novel therapeutic approaches for a number of chronic lung diseases.

Purinergic signaling in scarring

“…Although the persistence of inciting pathologic agents and the consequent chronic inflammatory state have been suggested to be prerequisites to different forms of pulmonary fibrosis, the situation is likely to be more complex for IPF, because of the poor efficacy of standard anti‐inflammatory therapies, including corticosteroids (47). In chronic obstructive pulmonary disease (COPD) consisting of chronic inflammation, oxidative stress, and bronchial obstruction, increased ECM deposition underlying the bronchial epithelium produces fibrosis and thickening of the airway wall (48).…”

Interferon‐γ‐induced insufficient autophagy contributes to p62‐dependent apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps

“…A number of factors, including pathogen infection, epithelial barrier impairment, allergy and immune dysregulation, and ostiomeatal unit obstruction, likely contribute to the pathogenesis of CRS . As airway epithelial barrier function is tightly interwoven with the ability to regulate the immune system, it may have important implications for CRS. The defect of sinonasal epithelial barrier function shown in nasal epithelial cell (NEC) damage and shedding has been documented in CRS .…”

Secretory IgA Deficiency in Individual Small Airways Is Associated with Persistent Inflammation and Remodeling

“…In addition to facilitating mucociliary clearance and responding to inhaled antigens and inflammatory stimuli (9,10), airway epithelium facilitates host defense by transporting IgA from the basolateral compartment to the airway surface (11,12). In small airways, IgA is produced locally by subepithelial plasma cells as polymeric IgA, which is then transported across airway epithelial cells via the polymeric immunoglobulin receptor (pIgR).…”