Lung airways barrier function

There are several approaches to evaluate lung toxicity in vitro, which aim on epithelial function, like transport, apical surface liquid homeostasis, and barrier function, rather than on cellular function, like inflammation, metabolism, or cell viability. Most of these approaches disturb the air-liquid interface. It is affirmed that changes in airway liquid surface volume affects transepithelial ion transport [5] and impacts pharmacological properties at least of ENaC [89],... 

Until recently, epithelial cells were considered to function solely as the ciliated barrier lining in the airways and as conduits for gas exchange at the air/blood interphase. As techniques have improved to isolate and culture these cells and measure their gene products, it has become clear that they have a key role in lung defense and repair. Epithelial cells secrete a number of anti-microbial compounds and immunoregulatory cytokines [52], and are also capable of ingesting and killing bacteria [53],... 

The lung contains more than 40 different types of cells, amongst which epithelial cells are vital for maintenance of the pulmonary blood-gas barrier. The epithelium also provides absorptive and secretive functions. The diversity of epithelial cell types is summarized as airway epithelium and alveolar epithelium cells. 

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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