Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia

Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR −/− pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defe...

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Bibliographic Details
Published in:Cell 2010-12, Vol.143 (6), p.911-923
Main Authors: Chen, Jeng-Haur, Stoltz, David A., Karp, Philip H., Ernst, Sarah E., Pezzulo, Alejandro A., Moninger, Thomas O., Rector, Michael V., Reznikov, Leah R., Launspach, Janice L., Chaloner, Kathryn, Zabner, Joseph, Welsh, Michael J.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Anions - metabolism
Cystic Fibrosis - metabolism
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Epithelium - metabolism
Humans
HUMDISEASE
Ion Transport
Respiratory System - metabolism
Respiratory System - pathology
Sus scrofa
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Summary:Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR −/− pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and tracheal/bronchial epithelia in tissues, cultures, and in vivo. CFTR −/− epithelia showed markedly reduced Cl - and HCO 3 - transport. However, in contrast to a widely held view, lack of CFTR did not increase transepithelial Na + or liquid absorption or reduce periciliary liquid depth. Like human CF, CFTR −/− pigs showed increased amiloride-sensitive voltage and current, but lack of apical Cl - conductance caused the change, not increased Na + transport. These results indicate that CFTR provides the predominant transcellular pathway for Cl - and HCO 3 - in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease. [Display omitted] ► Airway epithelia in a porcine model of cystic fibrosis lack Cl - and HCO 3 - transport ► In contrast to a widely held hypothesis, the CF epithelia do not hyperabsorb Na + ► Missing Cl - conductance causes voltage and current alterations seen in CF epithelia
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2010.11.029