AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 6 855-L864, Copyright © 1995 by American Physiological Society

ARTICLES

CFTR gene transfer corrects defective glycoconjugate secretion in human CF epithelial tracheal cells

M. Mergey, M. Lemnaouar, D. Veissiere, M. Perricaudet, D. C. Gruenert, J. Picard, J. Capeau, M. C. Brahimi-Horn and A. Paul
Institut National de la Sante et de la Recherche Medicale U 402, Faculte de Medecine Saint-Antoine, Paris, France.

We demonstrate that in immortalized normal human tracheal epithelial cells (NT-1 and 56FHTE8o-) 14C-labeled glycoconjugate secretion may be regulated independently by agonists of the protein kinase A (PKA) and protein kinase C (PKC) signaling pathways. In contrast, in immortalized cystic fibrosis (CF) human tracheal epithelial cells (CFT-1 and CFT-2), regulation is defective for agonists specific for the PKA but not for the PKC pathway. To characterize the involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) in regulated glycoconjugate secretion, we examined the effect of adenovirus-mediated gene transfer of CFTR to CF and control cells. Forty-eight hours after infection, at a multiplicity of infection of 50 plaque-forming units per cell, high levels of CFTR mRNA were detected by reverse transcription-polymerase chain reaction, and de novo synthesis of CFTR protein was demonstrated by immunoblotting. Gene transfer to CF cells restored defective adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretion not only of chloride but also of glycoconjugates. Taken together, these results argue for a role for CFTR in cAMP-mediated glycoconjugate secretion.

This article has been cited by other articles:

				C. A. Bertrand and R. A. Frizzell The role of regulated CFTR trafficking in epithelial secretion Am J Physiol Cell Physiol, July 1, 2003; 285(1): C1 - C18. [Abstract] [Full Text] [PDF]

				N. Chignard, M. Mergey, D. Veissiere, R. Poupon, J. Capeau, R. Parc, A. Paul, and C. Housset Bile salts potentiate adenylyl cyclase activity and cAMP-regulated secretion in human gallbladder epithelium Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G205 - G212. [Abstract] [Full Text] [PDF]

				F. Thevenod Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins Am J Physiol Cell Physiol, September 1, 2002; 283(3): C651 - C672. [Abstract] [Full Text] [PDF]

				K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]

				R. Kuver, J. H. Klinkspoor, W. R. A. Osborne, and S. P. Lee Mucous granule exocytosis and CFTR expression in gallbladder epithelium Glycobiology, February 1, 2000; 10(2): 149 - 157. [Abstract] [Full Text] [PDF]

				F. Becq, Y. Mettey, M. A. Gray, L. J. V. Galietta, R. L. Dormer, M. Merten, T. Metaye, V. Chappe, C. Marvingt-Mounir, O. Zegarra-Moran, et al. Development of Substituted Benzo[c]quinolizinium Compounds as Novel Activators of the Cystic Fibrosis Chloride Channel J. Biol. Chem., September 24, 1999; 274(39): 27415 - 27425. [Abstract] [Full Text] [PDF]

				W. Kammouni, B. Moreau, F. Becq, A. Saleh, A. Pavirani, C. Figarella, and M. D. Merten A Cystic Fibrosis Tracheal Gland Cell Line, CF-KM4 . Correction by Adenovirus-Mediated CFTR Gene Transfer Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 684 - 691. [Abstract] [Full Text]

				N. A. BRADBURY Intracellular CFTR: Localization and Function Physiol Rev, January 1, 1999; 79(1): 175 - 191. [Abstract] [Full Text] [PDF]

				J. M. PILEWSKI and R. A. FRIZZELL Role of CFTR in Airway Disease Physiol Rev, January 1, 1999; 79(1): 215 - 255. [Abstract] [Full Text] [PDF]

				A. P. Naren, M. W. Quick, J. F. Collawn, D. J. Nelson, and K. L. Kirk Syntaxin 1A inhibits CFTR chloride channels by means of domain-specific protein-protein interactions PNAS, September 1, 1998; 95(18): 10972 - 10977. [Abstract] [Full Text] [PDF]