Biosynthesis of glycosaminoglycans by thymic lymphocytes. Effects of mitogenic activation.

The immune response is regulated by cellular interactions involving thymus-derived lymphocytes. Even though evidence from several systems suggests that proteoglycans or their polysaccharide side chains, the glycosaminoglycans, are important mediators (modulators) of cellular interactions, little is known concerning the biosynthesis or possible functions of these macromolecules in lymphocytes. As an initial step in our systematic analyses of the complex arrays of protein saccharides of lymphocytes, the biosynthesis and secretion of glycosaminoglycans by both unstimulated and mitogenically activated lymphocytes have been investigated. Isolated thymic lymphocytes were labeled with D-[6-3H]-glucosamine and 35SO4(2-), and the amounts of radioactivity in each family of glycosaminoglycan or other types of saccharides were determined. The data indicate the following: (1) Lymphocytes synthesize and secrete substantial amounts of glycosaminoglycans. (2) Activated lymphocytes have greatly accelerated rates of secretion of glycosaminoglycans, which appear to be more highly sulfated than those of nonstimulated cells. (3) Sulfated glycosaminoglycans of lymphocytes consist largely of chondroitin 4-sulfates, with smaller amounts of heparan sulfates. (4) Lymphocyte stimulation results in a rapid and dramatic increase in the relative proportion of both cell-associated and cell-secreted chondroitin 6-sulfates. (5) Lymphocytes synthesize large proportions of an apparently unsulfated, glycosaminoglycan-like glycoconjugate which is resistant to sequential treatments degrading all known types of glycosaminoglycans. Taken together with previous work which indicates that exogenously added glycosaminoglycans are capable of altering lymphocyte functions, these data suggest that lymphocyte-derived glycosaminoglycans themselves may play an important role in modulating the cellular interactions which regulate the immune system.