Journal article
CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia
American journal of physiology. Lung cellular and molecular physiology, Vol.303(2), pp.L152-L160
07/15/2012
DOI: 10.1152/ajplung.00116.2012
PMCID: PMC3404631
PMID: 22637155
Abstract
A balance between alveolar liquid absorption and secretion is critical for maintaining optimal alveolar subphase liquid height and facilitating gas exchange in the alveolar space. However, the role of cystic fibrosis transmembrane regulator protein (CFTR) in this homeostatic process has remained elusive. Using a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we investigated ion transport properties and alveolar liquid transport in isolated type II alveolar epithelial cells (T2AECs) cultured at the air-liquid interface. CFTR was distributed exclusively to the apical surface of cultured T2AECs. Alveolar epithelia from CFTR
−/−
pigs failed to increase liquid absorption in response to agents that increase cAMP, whereas cAMP-stimulated liquid absorption in CFTR
+/−
epithelia was similar to that in CFTR
+/+
epithelia. Expression of recombinant CFTR restored stimulated liquid absorption in CFTR
−/−
T2AECs but had no effect on CFTR
+/+
epithelia. In ex vivo studies of nonperfused lungs, stimulated liquid absorption was defective in CFTR
−/−
alveolar epithelia but similar between CFTR
+/+
and CFTR
+/−
epithelia. When epithelia were studied at the air-liquid interface, elevating cAMP levels increased subphase liquid height in CFTR
+/+
but not in CFTR
−/−
T2AECs. Our findings demonstrate that CFTR is required for maximal liquid absorption under cAMP stimulation, but it is not the rate-limiting factor. Furthermore, our data define a role for CFTR in liquid secretion by T2AECs. These insights may help to develop new treatment strategies for pulmonary edema and respiratory distress syndrome, diseases in which lung liquid transport is disrupted.
Details
- Title: Subtitle
- CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia
- Creators
- Xiaopeng Li - Department of Internal Medicine, University of Iowa, Iowa City, IowaAlejandro P Comellas - Department of Internal Medicine, University of Iowa, Iowa City, IowaPhilip H Karp - Department of Internal Medicine, University of Iowa, Iowa City, IowaSarah E Ernst - Department of Internal Medicine, University of Iowa, Iowa City, IowaThomas O Moninger - Department of Internal Medicine, University of Iowa, Iowa City, IowaNicholas D Gansemer - Department of Internal Medicine, University of Iowa, Iowa City, IowaPeter J Taft - Department of Internal Medicine, University of Iowa, Iowa City, IowaAlejandro A Pezzulo - Department of Internal Medicine, University of Iowa, Iowa City, IowaMichael V Rector - Department of Internal Medicine, University of Iowa, Iowa City, IowaNathan Rossen - Department of Internal Medicine, University of Iowa, Iowa City, IowaDavid A Stoltz - Department of Internal Medicine, University of Iowa, Iowa City, IowaPaul B McCray - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaMichael J Welsh - Department of Internal Medicine, University of Iowa, Iowa City, IowaJoseph 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.303(2), pp.L152-L160
- DOI
- 10.1152/ajplung.00116.2012
- PMID
- 22637155
- PMCID
- PMC3404631
- NLM abbreviation
- Am J Physiol Lung Cell Mol Physiol
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- HL51670; HL091842; DK54759 / National Institutes of Health
- Language
- English
- Date published
- 07/15/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; ICTS; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
- Record Identifier
- 9984016712902771
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