Vitro Models of the Alveolar Epithelial Barrier

Keywords Pneumocytes Pulmonary drug delivery Pulmonary metabolism, Alveolar epithelium 

ACE Angiotensin-converting enzyme AEC Alveolar epithelial cell 

GABRP Gamma-aminobutyric acid receptor pi subunit 

The human alveolar epithelium consists of two cell types type I (alveolar epithelial type I [ATI], pneumocyte I) and type n (alveolar epithelial type II 

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. 

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Chapter 11 In Vitro Models of the Alveolar Epithelial Barrier 259... 

We used in vitro models of lung epithelial cell lines or primary cells to determine E25 permeability. Two different cell types were used to mimic the airway and alveolar epithelium of the lung to study transport. Calu-3, a human cell line derived from an airway carcinoma, when grown at an air/liquid interface, differentiate to form a secretory airway epithelium (17). Rat primary epithelial cells isolated as described by Cheek et al. (18) form a tight barrier similar in structure and function to the alveolar surface. Both cell types when grown to confluence form tight junctions and differentiate and polarize so that the apical or air surface has different characteristics than the basolateral or blood side. The typical transepithelial resistance observed was 350 or >1000 ohms-cm for Calu-3 cells or primary rat alveolar cells, respectively. Once an acceptable resistance was achieved, E25 (2 mg/mL) was placed in either the apical or the basolateral chamber. Cell monolayers were incubated at 37°C for up to 3 hours and ELISA measured the amount of E25 that translocated the epithelial layer and appeared in the receiver well. The apparent permeability (Papp) of the epithelium for E25 was calculated as ... 

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