Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense

Xiaopeng Li; Xiao Xiao Tang; Luis G Vargas Buonfiglio; Alejandro P Comellas; Ian M Thornell; Shyam Ramachandran; Philip H Karp; Peter J Taft; Kelsey Sheets; Mahmoud H Abou Alaiwa; Michael J Welsh; David K Meyerholz; David A Stoltz; Joseph Zabner

doi:10.1152/ajplung.00422.2015

Back

Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense

Journal article

Open access

Peer reviewed

Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense

Xiaopeng Li, Xiao Xiao Tang, Luis G Vargas Buonfiglio, Alejandro P Comellas, Ian M Thornell, Shyam Ramachandran, Philip H Karp, Peter J Taft, Kelsey Sheets, Mahmoud H Abou Alaiwa, …

American journal of physiology. Lung cellular and molecular physiology, Vol.310(7), pp.L670-L679

04/01/2016

DOI: 10.1152/ajplung.00422.2015

PMCID: PMC4824164

PMID: 26801568

Files and links (1)

url

https://doi.org/10.1152/ajplung.00422.2015View

Published (Version of record) Open Access

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.

Lung - pathology

Cystic Fibrosis - metabolism

Cells, Cultured

Male

Alveolar Epithelial Cells - metabolism

Alveolar Epithelial Cells - immunology

Cystic Fibrosis - immunology

Animals

Biological Transport

Bicarbonates - metabolism

Cystic Fibrosis Transmembrane Conductance Regulator - genetics

Female

Lung - metabolism

Sus scrofa

Lung - immunology

Hydrogen-Ion Concentration

Details

Title: Subtitle: Electrolyte transport properties in distal small airways from cystic fibrosis pigs with implications for host defense
Creators: Xiaopeng Li - Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Xiaopeng-Li@uiowa.edu
Xiao Xiao Tang - Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa
Luis G Vargas Buonfiglio - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Alejandro P Comellas - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Ian M Thornell - Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa
Shyam Ramachandran - Department of Pediatrics, University of Iowa, Iowa City, Iowa; and
Philip H Karp - Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Howard Hughes Medical Institute, Iowa City, Iowa
Peter J Taft - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Kelsey Sheets - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Mahmoud H Abou Alaiwa - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Michael J Welsh - 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
David K Meyerholz - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
David A Stoltz - 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
Joseph Zabner - Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.310(7), pp.L670-L679
DOI: 10.1152/ajplung.00422.2015
PMID: 26801568
PMCID: PMC4824164
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: American Physiological Society; United States
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 04/01/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Pathology; Neurosurgery; Internal Medicine
Record Identifier: 9984020504702771

Metrics

11 Record Views

44 Times Cited - Web of Science