Journal article
Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia
Cell (Cambridge), Vol.143(6), pp.911-923
2010
DOI: 10.1016/j.cell.2010.11.029
PMCID: PMC3057187
PMID: 21145458
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 HCO
3
- 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 HCO
3
- in porcine airway epithelia, and reduced anion permeability may initiate CF airway disease.
[Display omitted]
► Airway epithelia in a porcine model of cystic fibrosis lack Cl
- and HCO
3
- 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
Details
- Title: Subtitle
- Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia
- Creators
- Jeng-Haur Chen - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADavid A Stoltz - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAPhilip H Karp - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASarah E Ernst - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAAlejandro A Pezzulo - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAThomas O Moninger - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAMichael V Rector - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USALeah R Reznikov - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAJanice L Launspach - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAKathryn Chaloner - Department of Biostatistics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAJoseph Zabner - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAMichael J Welsh - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Cell (Cambridge), Vol.143(6), pp.911-923
- DOI
- 10.1016/j.cell.2010.11.029
- PMID
- 21145458
- PMCID
- PMC3057187
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013922702771
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