Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells
American Journal of Physiology - Lung cellular and Molecular Physiology
Previous studies in intact lung suggest that CFTR may play a role in cAMP regulated fluid transport from the distal airspaces of the lung. However, the potential contribution of different epithelial cells (alveolar epithelial type I, type II or bronchial epithelial cells) to CFTR regulated fluid transport is unknown. In this study we determined whether the CFTR gene is expressed in human lung alveolar epithelial type II (AT II) cells, and whether the CFTR chloride channel contributes to cAMP
... ulated fluid transport in cultured human AT II cells. Human AT II cells were isolated and cultured on collagen Icoated transwell membranes for 120-144 h with an air-liquid interface. The cultured cells retained typical AT II-like features based on morphologic studies. Net basal fluid transport was 0.89 ± 0.11 µl/cm 2 /h and increased to 1.35 ± 0.11 µl/cm 2 /h (mean±SE, n=18, P<0.05) by stimulation with cAMP agonists. The CFTR inhibitor, CFTR inh -172, inhibited cAMP stimulated but not basal fluid transport. In short-circuit current studies with an apical-to-basolateral transepithelial Clgradient, apical application of CFTR inh -172 reversed the forskolin-induced decrease in I sc . Real time RT-PCR demonstrated CFTR transcript expression in human AT II cells at a level similar to that in airway epithelial cells. We conclude that CFTR is expressed in cultured human AT II cells and may contribute to cAMP regulated apical-basolateral fluid transport. Nantz MH, Kurth MJ, Verkman AS, and Galietta LJ. CFTR activation in human bronchial epithelial cells by novel benzoflavone and benzimidazolone compounds. Am J Physiol Lung Cell Mol Physiol 285: L180-188, 2003. 6. Chen XJ, Eaton DC, and Jain L. Beta-adrenergic regulation of amiloridesensitive lung sodium channels. Am J Physiol Lung Cell Mol Physiol 282: L609-620, 2002. 7. Crandall ED and Matthay MA. Alveolar epithelial transport. Basic science to clinical medicine. Constitutive expression of MHC and adhesion molecules by alveolar epithelial cells (type II pneumocytes) isolated from human lung and comparison with immunocytochemical findings. J Cell Sci 107: 443-449, 1994. 9. Devor DC, Bridges RJ, and Pilewski JM. Pharmacological modulation of ion transport across wild-type and DeltaF508 CFTR-expressing human bronchial epithelia.