title: In vivo analysis of fluid transport in cystic fibrosis airway epithelia of bronchial xenografts.
abstract: An in vivo human bronchial xenograft model system was used to simultaneously analyze electrolyte and fluid transport defects in fully differentiated human cystic fibrosis (CF) and non-CF proximal airways. CF airways demonstrated three discernible defects when compared with non-CF, including 1) a lack of adenosine 3',5'-cylic monophosphate (cAMP)-inducible Cl- secretion, 2) a fourfold higher basal fluid absorption rate, and 3) an altered regulation of fluid absorption in response to amiloride-stimulated changes in Na+ transport. A unique finding in this study demonstrated that treatment of epithelia with amiloride led to a greater than threefold decrease in the rate of fluid absorption in CF tissues as contrasted to a greater than threefold increase in the rate of fluid absorption in non-CF tissues. The removal of apical Na+ from amiloride-treated non-CF xenografts was capable of ablating this amiloride-induced increase in fluid absorption. In light of the recent interactions demonstrated between CF transmembrane conductance regulator (CFTR) and the rat epithelial, amiloride-sensitive Na+ channel, these findings implicate additional complexities between the Na+ conductance pathways and fluid transport in normal and CF proximal airways. Such findings suggest that CFTR may also regulate amiloride-insensitive Na+ channels.
authors.affiliation: Institute for Human Gene Therapy, University of Pennsylvania Medical Center, Philadelphia, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Yankaskas
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.forename: J F
authors.initials: JF
authors.lastname: Engelhardt
mesh_terms: D000042:Absorption / Q000187:drug effects; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001826:Body Fluids / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism* / Q000502:physiology / Q000637:transplantation; D003550:Cystic Fibrosis / Q000378:metabolism*; D004594:Electrophysiology; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012964:Sodium / Q000502:physiology; D014183:Transplantation, Heterologous
chemical_list: D000584:Amiloride; D012964:Sodium