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Am J Physiol Lung Cell Mol Physiol 281: L713-L721, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 3, L713-L721, September 2001

Expression of CFTR and Clminus conductances in cells of pulmonary neuroepithelial bodies

Herman Yeger1, Jie Pan1, Xiao Wen Fu1, Christine Bear2, and Ernest Cutz1

Division of Pathology, Departments of 1 Pediatric Laboratory Medicine and Pathobiology and 2 Physiology and Cell Biology, Research Institute and Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada M5G 1X8

The pulmonary neuroendocrine cell system comprises solitary neuroendocrine cells and clusters of innervated cells or neuroepithelial bodies (NEBs). NEBs figure prominently during the perinatal period when they are postulated to be involved in physiological adaptation to air breathing. Previous studies have documented hyperplasia of NEBs in cystic fibrosis (CF) lungs and increased neuropeptide (bombesin) content produced by these cells, possibly secondary to chronic hypoxia related to CF lung disease. However, little is known about the role of NEBs in the pathogenesis of CF lung disease. In the present study, using a panel of cystic fibrosis transmembrane conductance regulator (CFTR)-specific antibodies and confocal microscopy in combination with RT-PCR, we demonstrate expression of CFTR message and protein in NEB cells of rabbit neonatal lungs. NEB cells expressed CFTR along with neuroendocrine markers. Confocal microscopy established apical membrane localization of the CFTR protein in NEB cells. Cl- conductances corresponding to functional CFTR were demonstrated in NEB cells in a fresh lung slice preparation. Our findings suggest that NEBs, and related neuroendocrine mechanisms, likely play a role in the pathogenesis of CF lung disease, including the early stages before establishment of chronic infection and chronic lung disease.

cystic fibrosis transmembrane conductance regulator; expression in neuroepithelial bodies; chloride


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