[HTML][HTML] Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia
JH Chen, DA Stoltz, PH Karp, SE Ernst, AA Pezzulo… - Cell, 2010 - cell.com
Cell, 2010•cell.com
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 …
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 …
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 HCO3- 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 HCO3- in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease.
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