Role of claudin interactions in airway tight junctional permeability.
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.
Coyne
Carolyn B
CB
Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Gambling
Todd M
TM
Boucher
Richard C
RC
Carson
Johnny L
JL
Johnson
Larry G
LG
D016475:3T3 Cells; D000818:Animals; D001980:Bronchi / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D062445:Claudin-1; D062465:Claudin-3; D062507:Claudin-5; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology*; D014162:Transfection
C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C107466:CLDN5 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062507:Claudin-5; C568113:Cldn1 protein, mouse; C568123:Cldn3 protein, mouse; C491511:Cldn5 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins