Biosynthesis of glycosaminoglycans by thymic lymphocytes. Effects of mitogenic activation

Abstract

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.

Comparative study on glycosaminoglycans synthesized in peripheral and peritoneal polymorphonuclear leucocytes from guinea pigs

“…Another noteworthy finding in the experiment is that peritoneal PMN leucocytes have greatly accelerated secretion of chondroitin 6-sulphate. This result conformed to the observation that glycosaminoglycans synthesized in mitogenically activated lymphocytes are different from those synthesized in non-stimulated cells (Hart, 1982); activated lymphocytes have accelerated secretion of glycosaminoglycans, which appear to be more highly sulphated than those of non-stimulated cells, and to be increased in the relative proportion of both cell-associated and cell-secreted chondroitin 6-sulphate in the total glycosaminoglycans. Furthermore, Vannucchi et al (1982) reported a change in the glycosaminoglycans involved in the activation of PMN leucocytes in adhesion culture.…”

Synthesis and distribution of glycosaminoglycans in human leukemic B‐ and T‐cells and monocytes studied using specific enzymic treatments and high‐performance liquid chromatography

“…It has been shown that human lymphocytes and monocytes produce various PG types (Kolset et al, 1983(Kolset et al, , 1984. Normal T-and B-lymphocytes predominantly synthesize CSPGs (Morris et al, 1989;McQuillan et al, 1989;Levitt and Ho, 1983) as well as HSPGs (25% of total PGs; Levitt and Ho, 1983;Wilson and Rider, 1991;Hart, 1982). Steward et al (1990) demonstrated that T-cells secrete CS chains to culture medium.…”

Effects of mitogens on synthesis and distribution of heparan and chondroitin sulphates by human leukemic B, T cells and monocytes studied by high‐performance liquid chromatography and radiochemical detection

“…Mitogenic substances has been reported to affect proliferation of leukemic cells of T, B and monocytic origin (Weiss et al, 1986;Papadogiannakis et al, 1986;Hart, 1982;Hadden, 1988). In the present work, their effect on the synthesis and distribution of GAGs, independently of cell proliferation, was studied.…”

“…Normal T and B lymphocytes predominantly synthesize CSPGs (Morris et al, 1989;McQuillan et al, 1989;Levitt and Ho, 1983) as well as HSPGs (Levitt and Ho, 1983;Wilson and Rider, 1991;Hart 1982). T lymphocytes secrete mainly 4-sulfated, CSPGs chains to culture medium (Steward et al, 1990), whereas B lymphocytes synthesize both 4-sulfated PGs and 6-sulfated CSPGs (Rider and Hart, 1987).…”