A Cystic Fibrosis Tracheal Gland Cell Line, CF-KM4: Correction by Adenovirus-Mediated CFTR Gene Transfer

作者：Wafa Kammouni, Bertrand Moreau, Frédéric Becq, Ali Saleh, Andréa Pavirani, Catherine Figarella, Marc D. Merten · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：1999 · DOI：10.1165/ajrcmb.20.4.3341 · 被引用次数：40 · 研究领域：Cystic Fibrosis Research Advances、Tracheal and airway disorders、Neonatal Respiratory Health Research

Human tracheal gland serous (HTGS) cells are now considered one principal pulmonary target for the gene therapy of cystic fibrosis (CF). We developed a CF tracheal gland serous cell line, CF-KM4, obtained by the transformation of primary cultures of CF tracheal gland serous cells homozygous for the DeltaF508 mutation by using the wild-type SV40 virus. This cell line retained epithelial and secretory features of the native CF-HTGS cells in primary culture, namely, presence of cytokeratin, constitutive secretion of secretory leukocyte proteinase inhibitor, absence of responsiveness to carbachol and isoproterenol, and defective cyclic adenosine monophosphate-dependent chloride channel activity. Adenovirus-mediated CF transmembrane conductance regulator (CFTR) gene transfer into CF-KM4 cells corrected the defective chloride channel activity as well as the responsiveness to adrenergic and cholinergic agonists. In contrast, control transfection using adenovirus-mediated beta-galactosidase gene transfer was totally ineffective. In conclusion, these results present a stable CF tracheal gland cell line that has retained its epithelial and CF-specific defective secretory characteristics which are corrected after CFTR gene transfer. This cell line therefore appears to be a useful tool for large-scale molecular and cellular pharmacologic investigations designed to test potential therapies of the disease CF.