Alveolar epithelial cells barrier properties

Alveolar epithelial cells (AECs) are connected with each other by various epithelial cell-cell contacts (i.e., tight junctions, adherens junctions and others). These contacts comprise several groups of proteins, such as occludin, zonula occludens (ZO-1, -2, -3), claudins, tricellulin, E-cadherin and intercellular adhesion molecule-1 (ICAM-1) [13-15], Their regulation and interplay, which has influence on epithelial barrier properties, however, is largely unknown to date. 

The primary cell culture model is a more valid model for the study of absorption and transport processes of a drug via the pulmonary route. It provides a tight epithelial barrier with morphological and functional properties resembling those of the in-vivo condition. Primary alveolar epithelial cells from rats [39], rabbits [40] and humans [41] which display morphological and biochemical characteristics similar to the native epithelium have been isolated and can be used for drug transport studies. 

Cell lines of both airway and alveolar epithelial origin are available (immortal cells, transformed or carcinoma-derived), the most commonly used being the CALU-3 cell line derived from airway epithelium [37], and the A549 cell line derived from a bronchioalveolar carcinoma [38]. However, these cultured cell lines share only limited similarity in morphology, biochemical characteristics, and barrier properties (low epithelial resistance due to the lack of tight junctions) with the epithelia in vivo. Consequently, the results of absorption and metabolism studies based on cultured cell lines should be interpreted with caution. 

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