Epithelial cell apical surfaces

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. 

Cilia are thin cylindrical hair-like structures with a cross-sectional radius of 0.1 gm projecting from the apical epithelial surface of ciliated columnar cells. Ciliary length is thought to correspond to periciliary fluid depth and range from approximately 7 gm in proximal airways to roughly 5 gm in more distal airways.- Each ciliated epithelial cell supports approximately 200 cilia at a density of eight cilia/gm. Short microvilli, possibly associated with secretory functions, are interspersed among the cilia. 

Figure 6, Polarized epithelial cells in culture. Epithelial cells in culture possess an apical surface with microvilli that faces the tissue culture medium (equivalent to the lumenal side of the cells in vivo), and a basolateral surface that faces the tissue culture dish (equivalent to the blood side of the cells in vivo).

Fig. 9 Schematic representation depicting the movement of molecules from the absorbing (mucosal or apical) surface of the GIT to the basolateral membrane and from there to blood. (A) transcellular movement through the epithelial cell. (B) Paracellular transport via movement between epithelial cells. (Q Specialized carrier-mediated transport into the epithelial cell. (D) Carrier-mediated efflux transport of drug out of the epithelial cell. (Copyright 2000 Saguaro Technical Press, Inc., used with permission.)...

The apical surface is loaded with more than 20 different digestive enzymes and proteins the protein lipid ratio is high 1.7 1 [63]. The half-life of these proteins is 6-12 h, whereas the epithelial cells last 2-3 days. So the cell must replace these constituents without depolarizing itself. The cytoskeleton may play a role... 

Figure 2.7 Schematic of the apical phospholipid hilayer surface of the epithelial cells, indicating three types of passive diffusion transcellular (la > 1 b 1 c), paracellular (2a >2b 2c), and the hypothesized lateral, under the skin of the tight junction (3a—> 3b—> 3c) modes. Tight-junction matrix of proteins highly stylized, based on Ref. 75. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Said et al. [78] directly measured the acid microclimate on the surface of gastrointestinal tract (GIT) epithelial cells (intact with mucus layer) in rats. The pH on the apical (donor) side of the cells varied from 6.0 to 8.0, while the pH on the basolateral (acceptor) side was 7.4. Furthermore, the pH gradient between... 

P-glycoprotein is not only expressed in tumor cells, but also in cells of several healthy tissues. In liver it was detected in the biliary canalicular surface of hepato-cytes and the apical surface of small biliary ductules. In the small intestine and colon, it is localized in the apical surface of columnar epithelial cells, and in kidneys it is found in the brush border membrane of proximal tubules. Moreover, it is detectable on the apical surface of small ductules in the pancreas and on the surface of cells in the medulla and cortex of adrenals [2]. 

The number of channels synthesized, processed, and trafficked to the apical membrane and rate of CFTR internalization at the apical membrane determine the cell surface density. Mutations in CFTR that alter one or more of these parameters decrease total CFTR-mediated anion flux and impair epithelial cell function. 

Many cells have an asymmetric structure because of the necessity for function (Drubin and Nelson, 1996). For example, (the outer surface of) the plasma membrane of epithelial cells is fenced by a tight junction so that the lipids are separated between the apical part and the basolateral part (Fig. 9) (Eaton and Simons, 1995). Therefore, some molecular mechanisms must exist to sort the plasma membrane proteins into these two parts. Some signals related to the secretory/endocytic pathways have been found important (Matter and Mellman, 1994). Their details are not described here because the area is too specific for predictive purposes. 

For AIC conditions, the apical surface of the epithelial cell layer is exposed to air after the nasal cells reached confluence on the Transwell insert, while the basolateral side is fed with culture fluid. Figure 9.3 shows TEER changes in epithelial cell layers cultured up to 20 days in LCC versus AIC methods [46], In AIC condition (initiated from day 3 after seeding), TEER peaked on day 5 and maintained above the TEER values observed for LCC counterparts. By contrast, TEER observed for LCC conditions peaked on day 2 and declined toward zero by day 15. These data indicate that human nasal epithelial cells at an air interface culture exhibit better electrophysiological characteristics than those cultured by the conventional liquid-covered conditions. 

Vitamin C (VC, L-ascorbic acid) is known to be essential for many enzymatic reactions. Sodium-dependent VC transporters (SVCT), SVCT1 and SVCT2, were recently identified and reported to be localised in the apical cell membrane of AECs in the lung of adult rats. These results suggest that SVCT proteins could transport the reduced form of VC from the airway/alveolar surface liquid into respiratory epithelial cells [106],... 

The situation is, however, different in the alveolar region of the lung where the respiratory gas exchange takes place. Its thin squamous epithelium is covered by the so-called alveolar surface liquid (ASL). Its outermost surface is covered by a mixture of phospholipids and proteins with a low surface tension, also often referred to as lung surfactant. For this surfactant layer only, Scarpelli et al. [74] reported a thickness between 7 and 70 nm in the human lung. For the thickness of an additional water layer in between the apical surface of alveolar epithelial cells and the surfactant film no conclusive data are available. Hence, the total thickness of the complete ASL layer is actually unknown, but is certainly thinner than 1 gm. 

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