Heterogeneity of claudin expression by alveolar epithelial cells.
Claudins are proteins that participate in epithelial barrier function and regulate paracellular permeability. By immunohistochemistry of adult rat lung sections, claudin-3, claudin-4, and claudin-5 were found to be co-expressed by type II alveolar epithelial cells. Claudin-3 and claudin-4 were also co-expressed by some alveolar epithelial cells adjacent to type II cells. In contrast, claudin-5 was expressed throughout the alveolus. Isolated primary rat alveolar epithelial cells in culture also expressed claudin-3, claudin-4, and claudin-5, but showed little claudin-1 and claudin-2 expression. Claudin expression by isolated cells at both the mRNA and protein level varied with time in culture. In particular, claudin-3 and claudin-5 co-localized and were distributed around the alveolar cell periphery, but claudin-4 expression was heterogeneous. We also found that paracellular permeability was increased when cultured alveolar epithelial cells were treated with a fatty acid amide, methanandamide. Methanandamide did not alter cell viability. Claudin-3, claudin-4, claudin-5, occludin, and zona occludens 1 remained localized to cell-cell contact sites at the plasma membrane in methanandamide-treated cells, suggesting that plasma membrane localization of these junction proteins is not sufficient for maintaining barrier function. However, methanandamide-treated cells showed a 12-fold increase in claudin-5 expression and a 2- to 3-fold increase in claudin-3, consistent with the notion that specific changes in claudin expression levels may correlate with changes in alveolar epithelial barrier function.
Wang
Fushan
F
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.
Daugherty
Brandy
B
Keise
Lisa L
LL
Wei
Zhangyong
Z
Foley
Joseph P
JP
Savani
Rashmin C
RC
Koval
Michael
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D057167:Claudins; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D001095:Arachidonic Acids; C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D057167:Claudins; C568113:Cldn1 protein, mouse; C568114:Cldn1 protein, rat; C491874:Cldn2 protein, rat; C568123:Cldn3 protein, mouse; C568124:Cldn3 protein, rat; C568158:Cldn4 protein, mouse; C491511:Cldn5 protein, mouse; C491510:Cldn5 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; C088155:methanandamide