title: Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense.
abstract: While pathological and clinical data suggest that small airways are involved in early cystic fibrosis (CF) lung disease development, little is known about how the lack of cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to disease pathogenesis in these small airways. Large and small airway epithelia are exposed to different airflow velocities, temperatures, humidity, and CO2 concentrations. The cellular composition of these two regions is different, and small airways lack submucosal glands. To better understand the ion transport properties and impacts of lack of CFTR function on host defense function in small airways, we adapted a novel protocol to isolate small airway epithelial cells from CF and non-CF pigs and established an organotypic culture model. Compared with non-CF large airways, non-CF small airway epithelia cultures had higher Cl(-) and bicarbonate (HCO3 (-)) short-circuit currents and higher airway surface liquid (ASL) pH under 5% CO2 conditions. CF small airway epithelia were characterized by minimal Cl(-) and HCO3 (-) transport and decreased ASL pH, and had impaired bacterial killing compared with non-CF small airways. In addition, CF small airway epithelia had a higher ASL viscosity than non-CF small airways. Thus, the activity of CFTR is higher in the small airways, where it plays a role in alkalinization of ASL, enhancement of antimicrobial activity, and lowering of mucus viscosity. These data provide insight to explain why the small airways are a susceptible site for the bacterial colonization.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Xiaopeng-Li@uiowa.edu.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa;
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Luis G
authors.initials: LG
authors.lastname: Vargas Buonfiglio
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Comellas
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa;
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thornell
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa; and.
authors.forename: Shyam
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa;
authors.forename: Philip H
authors.initials: PH
authors.lastname: Karp
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Taft
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Kelsey
authors.initials: K
authors.lastname: Sheets
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Abou Alaiwa
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.affiliation: Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: David K
authors.identifier: 0000-0003-1552-3253
authors.initials: DK
authors.lastname: Meyerholz
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa;
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
mesh_terms: D056809:Alveolar Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D034421:Sus scrofa
chemical_list: D001639:Bicarbonates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: cystic fibrosis transmembrane conductance regulator