Glycoproteins epithelial

IFNs are natural glycoproteins produced by the cells of most vertebrates in response to the challenge by foreign agents, such as infectious organisms (viruses, bacteria, fungi, and parasites), and by tumor cells. IFNs can be produced by cells of the innate and adaptive immune systems and by non-immune cells such as fibroblasts and epithelial cells. 

Both influx and efflux transporters are located in intestinal epithelial cells and can either increase or decrease oral absorption. Influx transporters such as human peptide transporter 1 (hPEPTl), apical sodium bile acid transporter (ASBT), and nucleoside transporters actively transport drugs that mimic their native substrates across the epithelial cell, whereas efflux transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP) actively pump absorbed drugs back into the intestinal lumen. 

Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997 94 2031-5. 

Mucins are a class of O-linked glycoproteins that are distributed on the surfaces of epithelial cells of the respiratory, gastrointestinal, and reproductive tracts. The Golgi apparatus plays a major role in glycosyla-tion reactions involved in the biosynthesis of glycoproteins. 

Okabe H., Okubo T. and Ochi Y. (1996). Expression of an epithelial membrane glycoprotein by neurons arising from the human olfactory plate through development. 

A Sparreboom, J van Asperen, U Mayer, AH Schinkel, JW Smit, DKF Meijer, P Borst, WJ Nooijen, JH Beijnen, O van Tillingen. Limited oral bioavailability of taxol and active epithelial secretion of pa-clitaxel (Taxol) caused by -glycoprotein in the intestine. Proc Nat Acad Sci USA 94 2031-2035, 1997. 

P Saha, J Yang, VHL Lee. (1998). Existence of a p-glycoprotein drug efflux pump in cultured rabbit conjunctival epithelial cells. Invest Opthalmol Vis Sci 39 1221-1226. 

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... 

Butcher, B.A., Gagliardo, L.F., ManWarren, T. and Appleton, J.A. (2000) Larvae-induced plasma membrane wounds and glycoprotein deposition are insufficient for Trichinella spiralis invasion of epithelial cells. Molecular and... 

McVay, C.S., Tsung, A. and Appleton, J.A. (1998) Participation of parasite surface glycoproteins in antibody-mediated protection of epithelial cells against TrichineUa spiralis. Infection and Immunity 66, 1941-1945. 

Kindon, H., Pothoulakis, C., Thim, L., Lynch-Devaney, K. and Podolsky, D.K. (1995) Trefoil peptide protection of intestinal epithelial barrier function cooperative interaction with mucin glycoprotein. Gastroenterobgy 109, 516-523. 

T., Simmons, N. L., Hirst, B. H., Functional expression of P-glycoprotein in apical membranes of human intestinal epithelial Caco-2 cells kinetics of vinblastine secretion and interaction with modulators, J. Biol. Chem. 1993, 268, 14991-14997. 

N. L., Drugs absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers, Pharm. Res. 1993, 10, 743-749. 

J., Artursson, P., Transport of celiprolol across human intestinal epithelial (Caco-2) cells mediation of secretion by multiple transporters including P-glycoprotein, Br. J. Pharmacol. 1993, 3 30, 1009-1016. 

P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. 

A. H., Meijer, D. K., Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type 1) and bulky (type 2) cationic drugs, J. Pharmacol. Exp. Ther. 1998, 286, 321— 327. 

N., Komano, T., Hori, R., Transport of digoxin by human P-glycoprotein expressed in porcine kidney epithelial cell line (LLC-PK1), J. Pharmacol. Exp. Ther. 1992, 263, 840-845. 

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 tissue distribution of P-glycoprotein yields important clues to its function. In most tissues it is localized to the apical (luminal) membrane of polarized epithelial cell layers. This location suggests that P-glycoprotein extrudes its substrates from the epithelial cells into the adjacent lumen. It is anticipated that P-glycopro-tein plays an important role as a protective mechanism against naturally occur-... 

Rao W, Dahlheimer JL, Bardgett ME, Snyder AZ, Finch RA, Sartorelli AC et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidmg resistance-associated protein contribute to the blood-cerebrospinalfluid drug-permeability barrier. Proc Natl Acad Sci USA 1999 96(7) 3900-3905. 

Langer RC, Riggs MW Cryptosporidium parvum apical complex glycoprotein CSL contains a sporozoite ligand for intestinal epithelial cells. Infect Immun 1999 67 5282-5291. 

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