Effect of mitogen and lymphokine stimulation on proteoglycan synthesis by lymphocytes

Abstract

The ability of mouse thymocytes and peripheral blood lymphocytes from rats to synthesize and secrete proteoglycans in the presence of a variety of mitogens and lymphokines was studied in vitro, and it was confirmed that such lymphocytes synthesize and secrete significant quantities of proteoglycans. Mitogenic stimulation of the cells with phytohaemagglutanin (PHA) induced a fourfold increase in proteoglycan synthesis; stimulation with interleukin-1 stimulated proteoglycan synthesis up to fivefold. Proteoglycan synthesis could also be stimulated by culturing the cells in the presence of interleukin-2. To determine if this response was related to cell proliferation, the cells were cultured in the presence of PHA and either cyclosporine or prostaglandin E2, two agents that inhibit lymphocyte proliferation. Under these conditions, proteoglycan synthesis remained elevated, indicating that this effect may be independent of cell proliferation. Chemical analysis of the proteoglycans indicated them to be composed of chondroitin sulfate and heparan sulfate. Their molecular size was small compared with cartilage proteoglycans but similar to the small dermatan sulfate proteoglycans synthesized by fibroblasts. On the basis of molecular size, three proteoglycan population were identified, and their relative proportions were altered by mitogenic stimulation of the cells. Taken together, these findings imply that proteoglycan synthesis is intimately associated with lymphocyte activation and may be related to cellular function in immune responses.

Modulation of macrophage and B cell function by glycosaminoglycans

“…It is interesting that administration of metalloprotease inhibitors has been shown to diminish symptoms in patients with this disease process [46]. Another mechanism that may increase the availability of glycosaminoglycans is an increase in glycosaminoglycan synthesis [47,48] or composition stimulated by local cytokines [49,50].…”

Glycosaminoglycans in Gingival Crevicular Fluid of Patients With Periodontal Class II Furcation Involvement Before and After Guided Tissue Regeneration. A Pilot Study

“…[13][14][15][16] Alternatively, its presence may reflect the gradual maturation of the healing tissues and associated infiltration with inflammatory cells which release chondroitin sulfate. [22][23][24] Irrespective of its source, it appears that once the chondroitin sulfate levels return close to the baseline levels noted prior to surgery, then the tissues may well have reached sufficient maturity to warrant second-stage surgery and membrane removal. Although not addressed in this study, it would be interesting to determine whether poor healing responses (due to infection or other causes) might be reflected in an absence of this "rebound" phenomenon of chondroitin sulfate.…”

Molecular and cell biology of the gingiva

“…Such a contrasting finding to the massive loss of collagen from the same tissues may be explained by the contribution of stimulated fibroblasts at the periphery of the inflammatory lesion, together with the contribution of proteoglycan content and products of the inflammatory cells. Indeed, the principal proteoglycan synthesized by inflammatory cells contains chondroitin sulfate (17); thus the presence of such proteoglycans could explain why chondroitin sulfate levels increase at the expense of dermatan sulfate in inflamed gingival tissues.…”