Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region

Epithelial cells are important components of the thymus microenvironment an d are involved in thymocyte differentiation. The production and secretion o f sulfated glycosaminoglycans by these cells grown in culture were investig ated using labeling with radioactive S-35-Na2SO4 and H-3-glucosamine. The m ajor glycosaminoglycans synthesized by these cells are heparan sulfate and hyaluronic acid. The structure of the heparan sulfate was investigated by t he pattern of degradation products formed by deaminative cleavage with nitr ous acid. The ratio S-35-sulfate/H-3-glucosamine is high in the segments of the heparan sulfate released during the deaminative cleavage with nitrous acid bur low in the resistant portion of the molecule. Thus, the heparan su lfate synthesized by the thymic epithelial cells contains a highly sulfated region. Digestion with heparitinase reveals that this highly sulfated regi on is a heparin-like segment of the molecule. The heparan sulfate is rapidl y incorporated into the cell surface but its secretion to the extracellular medium requires a longer incubation period. Finally, heparin was used to m imic the possible effect of this heparan sulfate with a highly sulfated reg ion, as ascertained by its ability to modulate thymocyte adhesion to thymic epithelial cells. Since heparin actually enhanced thymocyte adhesion, it i s suggested that the heparan sulfate described herein, secreted by the thym ic epithelium, may play a role upon intrathymic heterotypic cellular intera ctions. (C) 1999 Wiley-Liss, Inc.