title: Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region.
abstract: Epithelial cells are important components of the thymus microenvironment and are involved in thymocyte differentiation. The production and secretion of sulfated glycosaminoglycans by these cells grown in culture were investigated using labeling with radioactive 35S-Na2SO4 and 3H-glucosamine. The major glycosaminoglycans synthesized by these cells are heparan sulfate and hyaluronic acid. The structure of the heparan sulfate was investigated by the pattern of degradation products formed by deaminative cleavage with nitrous acid. The ratio 35S-sulfate/ H-glucosamine is high in the segments of the heparan sulfate released during the deaminative cleavage with nitrous acid but low in the resistant portion of the molecule. Thus, the heparan sulfate synthesized by the thymic epithelial cells contains a highly sulfated region. Digestion with heparitinase reveals that this highly sulfated region is a heparin-like segment of the molecule. The heparan sulfate is rapidly incorporated into the cell surface but its secretion to the extracellular medium requires a longer incubation period. Finally, heparin was used to mimic the possible effect of this heparan sulfate with a highly sulfated region, as ascertained by its ability to modulate thymocyte adhesion to thymic epithelial cells. Since heparin actually enhanced thymocyte adhesion, it is suggested that the heparan sulfate described herein, secreted by the thymic epithelium, may play a role upon intrathymic heterotypic cellular interactions.
authors.affiliation: Hospital Universitário and Department de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: Werneck
authors.forename: A J
authors.initials: AJ
authors.lastname: Oliveira-Dos-Santos
authors.forename: L C
authors.initials: LC
authors.lastname: Silva
authors.forename: D M
authors.initials: DM
authors.lastname: Villa-Verde
authors.forename: W
authors.initials: W
authors.lastname: Savino
authors.forename: P A
authors.initials: PA
authors.lastname: Mourão
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000096:biosynthesis / Q000378:metabolism; D004796:Clinical Enzyme Tests; D004187:Disaccharides / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D013455:Sulfur / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013950:Thymus Gland / Q000166:cytology*; D013997:Time Factors; D014316:Tritium
chemical_list: D002809:Chondroitin Sulfates; D004187:Disaccharides; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D009844:Oligosaccharides; D011133:Polysaccharide-Lyases; D013455:Sulfur; D013462:Sulfur Radioisotopes; D014316:Tritium; C021349:heparitinsulfate lyase