title: Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA.
authors.forename: Jeng-Haur
authors.initials: JH
authors.lastname: Chen
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.forename: Philip H
authors.initials: PH
authors.lastname: Karp
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ernst
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Moninger
authors.forename: Michael V
authors.initials: MV
authors.lastname: Rector
authors.forename: Leah R
authors.initials: LR
authors.lastname: Reznikov
authors.forename: Janice L
authors.initials: JL
authors.lastname: Launspach
authors.forename: Kathryn
authors.initials: K
authors.lastname: Chaloner
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000838:Anions / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D017136:Ion Transport; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology*; D034421:Sus scrofa
chemical_list: D000838:Anions; D019005:Cystic Fibrosis Transmembrane Conductance Regulator