Heterogeneity of claudin expression by alveolar epithelial cells

Am J Respir Cell Mol Biol. 2003 Jul;29(1):62-70. doi: 10.1165/rcmb.2002-0180OC. Epub 2003 Jan 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Arachidonic Acids / pharmacology
  • Cell Membrane Permeability / drug effects
  • Cells, Cultured
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Claudins
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Membrane Proteins / drug effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy, Fluorescence
  • Pulmonary Alveoli / cytology
  • Pulmonary Alveoli / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction


  • ABCA3 protein, human
  • ATP-Binding Cassette Transporters
  • Arachidonic Acids
  • CLDN1 protein, human
  • CLDN2 protein, human
  • CLDN3 protein, human
  • CLDN4 protein, human
  • Claudin-1
  • Claudin-3
  • Claudin-4
  • Claudin-5
  • Claudins
  • Cldn1 protein, mouse
  • Cldn1 protein, rat
  • Cldn2 protein, rat
  • Cldn3 protein, mouse
  • Cldn3 protein, rat
  • Cldn4 protein, mouse
  • Cldn5 protein, mouse
  • Cldn5 protein, rat
  • Membrane Proteins
  • RNA, Messenger
  • methanandamide