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Vol. 16, Issue 5, 2154-2167, May 2005
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F508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia
* Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248;
Mayo Foundation, S. C. Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, AZ 85259
Submitted November 17, 2004;
Revised January 31, 2005;
Accepted February 9, 2005
Monitoring Editor: Keith Mostov
Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and 
F508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of F508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No F508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of F508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and F508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.
Abbreviations used: ASL, airway surface liquid; AQP5, aquaporin 5; CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; F508; F, phenylalanine508 deletion; DIC, differential interference contrast; ERM, ezrin-radixin-moesin; EBP50, ERM binding protein50; Isc, short circuit current; IBMX, 3-isobutyl-1-methylxanthine; ISH, in situ hybridization; LCM, laser confocal microscopy; NL, normal; PM, plasma membrane; Rte, transepithelial resistance; Vte, transepithelial voltage.
These authors contributed equally to this work.
Address correspondence to: Silvia M. Kreda (silkre{at}med.unc.edu).
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