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Am J Physiol Lung Cell Mol Physiol 285: L1166-L1178, 2003. First published August 8, 2003; doi:10.1152/ajplung.00182.2003
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Role of claudin interactions in airway tight junctional permeability

Carolyn B. Coyne,1,2 Todd M. Gambling,3 Richard C. Boucher,1,4 Johnny L. Carson,1,3,4 and Larry G. Johnson1,2,4

1Cystic Fibrosis/Pulmonary Research and Treatment Center, Departments of 2Pharmacology and 4Medicine, and 3Center for Environmental Medicine and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Submitted 6 June 2003 ; accepted in final form 3 August 2003

Airway epithelial tight junctions (TJs) serve to separate the external and internal environments of the lung. However, the members of the claudin family that mediate this function have not been fully delineated. We characterized the claudin expression in normal airways removed from human donors during lung transplantation and determined the contribution of each claudin to airway barrier function. Stable cell lines in NIH/3T3 and human airway (IB3.1) cells were constructed expressing the claudin components found in the human airway, claudin-1, -3, or -5. The effects of claudin expression on transepithelial resistance, permeability coefficients, and claudin-claudin interactions were assessed. Claudin-1 and -3 decreased solute permeability, whereas claudin-5 increased permeability. We also detected oligomerization of claudin-5 in cell lines and in freshly excised human airways. Coimmunoprecipitation studies revealed heterophilic interactions between claudin species in both cell lines and human airway epithelium. These suggest that airway TJs are regulated by claudinclaudin interactions that confer the selectivity of the junction.

tight junction; perfluorooctanoic acid; freeze-fracture



Address for reprint requests and other correspondence: L. G. Johnson, Cystic Fibrosis/Pulmonary Research and Treatment Center, 7123A Thurston Bowles Bldg., CB#7248, UNC-CH, Chapel Hill, NC 27599-7248 (E-mail: Larry_Johnson{at}med.unc.edu).




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