Purification of a glycosaminoglycan-stimulatory lymphokine from supernatants of in vitro-activated human mononuclear cells

Glycosaminoglycans (GAGs), like collagens, are the major component of the connective tissue matrix. Fibroblasts are responsible for the production and maintenance of this matrix. Glycosaminoglycan-stimulatory factor (GAG-SF) from T lymphocytes is a lymphokine that selectively increases GAG synthesis in normal human dermal fibroblasts. Supernatants of mononuclear cells activated with a mitogen, concanavalin A, were used to purify GAG-SF to an apparent homogeneity. The GAG-SF proved to be a glycoprotein with a molecular weight of 67,000 and pI of 5.6. It was not mitogenic to fibroblasts and did not regulate collagen synthesis in confluent fibroblast cultures. The purified factor was distinct from interleukin-1 (IL-1), but it could synergize with IL-1, which was present in unpurified supernatants, in modulating the activation of fibroblasts. The purification and characterization of this lymphokine are important because it is a product of activated lymphocytes and thus may be involved in the immunopathogenesis of several human diseases characterized by the presence of lymphoid infiltrates in the target organ such as autoimmune diseases of the connective tissue, the stromal reactions in human tumors, and the fibrosis associated with chronic rejection of transplanted organs.