Poster abstracts
Poster number 79 submitted by Jack Wellmerling
Reduced Expression of the Ion Channel Cystic Fibrosis Transmembrane Conductance Regulator Leads to Increased Disease Severity in a Cigarette Smoke-Induced Mouse Model of Emphysema
Jack Wellmerling, Sheng-Wei Chang, Eunsoo Kim, Haley Steiner (Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University), Michael Borchers (Department of Internal Medicine, College of Medicine, University of Cincinnati), Prosper Boyaka, Estelle Cormet-Boyaka (Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University)
Abstract:
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world. It is a chronic inflammatory disease with no cure which ultimately results in death from respiratory failure. The two main components of the disease are chronic bronchitis and emphysema. Chronic bronchitis refers to the restriction of airflow as a result of smooth muscle constriction, mucus hypersecretion, and fibrosis of the primary airways. Emphysema refers to poor gas exchange in the lung parenchyma due to destruction of the alveolar tissue. Approximately 90% of COPD cases can be attributed to tobacco smoking. One particular ion channel, the cystic fibrosis transmembrane conductance regulator (CFTR), may offer attractive treatment options as a therapeutic target for COPD patients with chronic bronchitis. Previous studies from our group and others have shown decreased CFTR protein expression in the bronchial epithelium of COPD patients. We also reported that cigarette smoke exposure decreases CFTR expression and function in primary human bronchial cells and the human bronchial epithelial cell line 16HBE. CFTR plays a critical role in the lung where it maintains proper airway hydration and mucus viscosity by transporting chloride and bicarbonate ions across the bronchial epithelium. However, the role of this channel in the alveoli is less clear. To assess the effect of CFTR expression levels on sensitivity to cigarette smoke, we exposed wild-type, cftr+/-, and cftr-/- mice to cigarette smoke using the whole-body exposure method. Cftr+/- and cftr-/- mice displayed increased severity of emphysema compared to wild-type mice after 10 months of cigarette smoke exposure, quantified histologically by calculating the mean linear intercept. Our findings demonstrate for the first time that reduced CFTR expression increases alveolar destruction after exposure to cigarette smoke. Therefore, people carrying a mutation in the cftr gene might be more susceptible to tobacco smoke-induced emphysema.
Keywords: COPD, Smoke, CFTR