Restoration of Cyclic Adenosine Monophosphate–Stimulated Chloride Channel Activity in Human Cystic Fibrosis Tracheobronchial Submucosal Gland Cells by Adenovirus-Mediated and Cationic Lipid–Mediated Gene Transfer

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Abstract
In human airways, the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is predominantly expressed in serous cells of the tracheobronchial glands. Despite considerable evidence that submucosal glands are important contributors to the pathophysiology of CF lung disease, most attempts at CFTR gene transfer have primarily targeted airway surface epithelial cells. In this study, we systematically evaluated CFTR gene transfer into cultures of immortalized CF human tracheobronchial submucosal gland (6CFSMEO) cells using adenovirus and cationic lipid vectors. We found that the efficiency of adenovirus-mediated gene transfer was comparable in 6CFSMEO and CFT1 cells (a surface airway epithelial cell line isolated from a subject with CF). So was the ranking order of adenovirus vectors containing different enhancers/promoters (CMV >> E1a ∼ phosphoglycerokinase), as determined by both X-Gal staining and quantitative measurement of β-galactosidase activity. Further, we provide the first demonstration tha...