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

SummaryDefective 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (101 K)Download as PowerPoint slideHighlights► Airway epithelia in a porcine model of cystic fibrosis lack Cl- and HCO3- 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