Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro.
Cystic fibrosis (CF) is caused by the loss of functional CFTR Cl- channels. However, it is not understood how this defect disrupts salt and liquid movement in the airway or whether it alters the NaCl concentration in the thin liquid film covering the airway surface. Using a new approach, we found that CF airway surface liquid had a higher NaCl concentration than normal. Both CF and non-CF epithelia absorbed salt and liquid; however, expression of CFTR Cl- channels was required for maximal absorption. Thus, loss of CFTR elevates the salt concentration in CF airway surface liquid and in sweat by related mechanisms; the elevated NaCl concentration is due to a block in transcellular Cl- movement. The high NaCl may predispose CF airways to bacterial infections by inhibiting endogenous antibacterial defenses.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
J
J
Zabner
J J
JJ
Smith
P H
PH
Karp
J H
JH
Widdicombe
M J
MJ
Welsh
D000042:Absorption; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001980:Bronchi / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D009297:Nasal Mucosa / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D009994:Osmolar Concentration; D012016:Reference Values; D012965:Sodium Chloride / Q000378:metabolism*; D014132:Trachea / Q000473:pathology / Q000503:physiopathology
C505032:CFTR protein, human; D002712:Chlorides; C013407:benzamil; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D012965:Sodium Chloride; D000584:Amiloride; D000242:Cyclic AMP