Airway surface liquid layer

Airway cross-sections have the nominal anatomy shown in Fig. 5.16. Airway surface liquid (AST), primarily composed of mucus gel and water, surrounds the airway lumen with a thickness thought to vary from 5 to 10 mm. AST lies on the apical surface of airway epithelial cells (mostly columnar ciliated epithelium). This layer of cells, roughly two to three cells thick in proximal airways and eventually thinning to a single cell thickness in distal airways, rests along a basement membrane on its basal surface. Connective tissue (collagen fibers, basement membranes, elastin, and water) lies between the basement membrane and airway smooth muscle. Edema occurs when the volume of water within the connective tissue increases considerably. Interspersed within the smooth muscle are respiratory supply vessels (capillaries, arteriovenous anastomoses), nerves, and lymphatic vessels. 

Epiphase Airway surface liquid gel layer composed of mucins in the form... 

Airway surface liquid (ASL) is the very thin fluid layer (<7 (llM) maintained at the apical membrane of airway epithelia. ASL thickness is maintained by a tight control of fluid reabsorption and/or secretion, mediated by sodium and/or chloride channels. 

In the various regions of the respiratory tract different physiological mechanisms exist to remove foreign material. In the extra-thoracic airways, the trachea and the bronchi there is a thick liquid lining and the synchronous movement of microscopic hairy cila at the surface of the bronchial epithelial cells rapidly moves deposited particles toward the larynx, where they are swallowed (mucociliary clearance). Normally this takes 1-3 days. Only highly soluble material moving from the air into the liquid layer will have systemic access via the blood. 

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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