Impermeable epithelial cells

Attempts to study the entry of ES products into cells using markers of fluid phase endocytosis yielded unexpected results. When larvae browse resistant IEC-6 cells in the presence of extracellular fluorescent dextran, dextran enters the cytoplasm of a significant proportion of the cells in the mono-layer (Butcher et al., 2000). The parameters of dextran entry are most compatible with the conclusion that larvae wound the plasma membranes of IEC-6 cells that is, they create transient breaches in the membrane that allow impermeant markers to enter the cell (McNeil and Ito, 1989). Wounding is considered to be a common occurrence in intestinal epithelia (McNeil and Ito, 1989). Injured cells are able to heal their wounds by recruiting vesicles to seal the breach (Steinhardt et al., 1994). In an experimental system, healing allows the injured cell to retain cytoplasmic dextran. In epithelial cell cultures inoculated with T. spiralis larvae, the relationship between glycoprotein delivery and injury of plasma membranes is not clear, i.e. dextran-laden cells do not always stain with Tyv-specific antibodies and... 

As the filtrate flows into the descending limb of this loop, the NaCl concentration in the fluid surrounding the tubule increases by a factor of four, and osmotic processes cause water to be reabsorbed. At the same time, salts and metabolic products are secreted into the tubular fluid. In the ascending limb, in contrast, the tubular wall is nearly impermeable to water. Here, the epithelial cells contain molecular pumps that transport sodium and chloride from the tubular fluid into the space between the nephrons (the interstitium). These processes are accounted for in considerable detail in the spatially extended model developed by Holstein-Rathlou et al. [14]. In the present model, the reabsorption l rmh in the proximal tubule and the flow resistance Rum are treated as constants. Without affecting the composition much, the proximal tubule reabsorbs close to 60% of the ultrafiltrate produced by the glomerulus. 

Epithelial cells normally exhibit polarity (Chapter 2) and this is generally not obvious when they are attached to an impermeable plastic surface. Millipore and Costar each produce inserts for 6-well and 24-well tissue culture trays (Fig. 3.2b) which allow the cells to attach to a semi-permeable membrane and to contact the medium on both apical and basolateral surfaces. The medium inside the insert (apical surface) does not mix with the medium in the well outside the insert and Costar s Transwell is designed to allow sampling of the two compartments with the insert in place. 

The plasma membrane of epithelial cells, in common with other cell types, is selectively permeable, allowing the penetration of some substances but not others. The construction of the membrane from amphipathic lipid molecules forms a highly impermeable barrier to most polar and charged molecules, thereby preventing the loss of most water-soluble contents of the cell. This selective permeability presents a physical barrier to drag absorption, limiting absorption to specific routes and mechanisms, as described below (see Section 1.3.3). 

A simple experiment demonstrates the impermeability of certain tight junctions to many water-soluble substances. In this experiment, lanthanum hydroxide (an electron-dense colloid of high molecular weight) is injected into the pancreatic blood vessel of an experimental animal a few minutes later, the pancreatic acinar cells, which are specialized epithelial cells, are fixed and prepared for microscopy. As shown In Figure 6-10, the lanthanum hydroxide diffuses from the blood Into the space that separates the lateral surfaces of adjacent acinar cells, but cannot penetrate past the tight junction. 

A EXPERIMENTAL FIGURE 6-10 Tight junctions prevent passage of large molecules through extracellular space between epithelial cells. This experiment, described in the text, demonstrates the impermeability of tight junctions in the pancreas to the large water-soluble colloid lanthanum hydroxide. [Courtesy of D. Friend.]... 

The lens presents in the periphery, at least in the eye of frog and rat, superficial epithelial cells adjoined by TJ impermeable to lanthanum and horseradish peroxides (HRP) tracer, while the equatorial region is permeable and represents the major site of efilux and influx (Lo 1987). 

In a study of guinea-pig cecal epithelium, Mora-Galindo (Mora-Galindo 1986) showed that cells at the surface and in middle regions of crypts possess TJ impermeable to lanthanum, whereas junctions between cells located at the bottom of crypts often were permeable to the tracer, indicating that permeability decreases as the epithelial cells mature. 

Pure phospholipid bilayers are essentially impermeable to water, but most cellular membranes contain water-channel proteins that facilitate the rapid movement of water in and out of cells. Such movement of water across the epithelial layer lining the kidney tubules of vertebrates is responsible for concentrating the urine. If this did not happen, one would excrete several liters of urine a day In higher plants, water and minerals are absorbed from the soil by the roots and move up the plant through conducting tubes (the xylem) water loss from the plant, mainly by evaporation... 

The skin covers a surface area of more than 1 m and is the most readily accessible organ in terms of drug delivery. However, the skin is also the most impermeable of all the epithelial membranes, and, owing to the multiple layers of homy cells in the stratum comeum, it is an excellent barrier to the penetration of hydrophilic substances. Therefore, the rate of passive permeation of proteins is far too slow to be therapeutically significant. 

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