Document Detail


CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia.
MedLine Citation:
PMID:  22637155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Xiaopeng Li; Alejandro P Comellas; Philip H Karp; Sarah E Ernst; Thomas O Moninger; Nicholas D Gansemer; Peter J Taft; Alejandro A Pezzulo; Michael V Rector; Nathan Rossen; David A Stoltz; Paul B McCray; Michael J Welsh; Joseph Zabner
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-25
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-16     Completed Date:  2012-09-20     Revised Date:  2014-10-10    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L152-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Absorption
Animals
Biological Transport
Cell Polarity
Cells, Cultured
Chlorides / metabolism
Cyclic AMP / physiology
Cystic Fibrosis Transmembrane Conductance Regulator / genetics,  metabolism,  physiology*
Electric Impedance
Extravascular Lung Water / metabolism*,  secretion
Female
Gene Knockout Techniques
Male
Pneumocytes / metabolism*,  physiology,  secretion
Pulmonary Alveoli / cytology,  metabolism,  secretion
Surface Tension
Sus scrofa
Tight Junctions / metabolism
Grant Support
ID/Acronym/Agency:
DK54759/DK/NIDDK NIH HHS; HL091842/HL/NHLBI NIH HHS; HL51670/HL/NHLBI NIH HHS; K01 HL080966/HL/NHLBI NIH HHS; P30 ES005605/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Chlorides; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; E0399OZS9N/Cyclic AMP
Comments/Corrections
Comment In:
Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L489-91   [PMID:  22797251 ]

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