Roles for claudins in alveolar epithelial barrier function

• Type of Material: Article
• Authors: Christian E. Overgaard, Emory University; Leslie A. Mitchell, Emory University; Michael H Koval, Emory University
• Language: English
• Date: 2012-06
• Publisher: New York Academy of Sciences
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 New York Academy of Sciences.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2012.06545.x/abstract
• Title of Journal or Parent Work: Annals of the New York Academy of Sciences
• ISSN: 0077-8923
• Volume: 1257
• Issue: 1
• Start Page: 167
• End Page: 174
• Grant/Funding Information: This work was supported by Emory Alcohol and Lung Biology Center/National Institutes of Health (NIH) grants P50-AA013757 (M.K.), R01-HL083120 (M.K.), AA-013528 (to C.E.O. and L.A.M.) and by the Emory University Research Committee (M.K.).
• Keywords: alcoholic lung disease; acute respiratory distress syndrome; tight junction; sepsis; acute lung injury
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery

Abstract

Terminal airspaces of the lung, alveoli, are sites of gas exchange which are sensitive to disrupted fluid balance. The alveolar epithelium is a heterogeneous monolayer of cells interconnected by tight junctions at sites of cell-cell contact. Paracellular permeability depends on claudin-family tight junction proteins. Of over a dozen alveolar claudins, cldn-3, cldn-4 and cldn-18 are the most highly expressed; other prominent alveolar claudins include cldn-5 and cldn-7. Cldn-3 is primarily expressed by type II alveolar epithelial cells whereas cldn-4 and cldn-18 are expressed throughout the alveolar epithelium. Lung diseases associated with pulmonary edema, such as alcoholic lung syndrome and acute lung injury affect alveolar claudin expression which is frequently associated with impaired fluid clearance due to increased alveolar leak. However, recent studies have identified a role for increased cldn-4 in protecting alveolar barrier function following injury. Thus, alveolar claudins are dynamically regulated, tailoring lung barrier function to control the air-liquid interface.