Connective tissue activation. XXVII. The behavior of skin fibroblasts from patients with scleroderma

Four normal (NF) and 4 scleroderma skin fibroblast (SF) strains were compared with respect to 1) basal 14C-glucosamine and 35SO4-labeled glycosaminoglycan (GAG) synthesis, 2) responsiveness to autacoid mediators, and 3) performance following maximal stimulation. Under basal conditions, SF synthesized and secreted 2-3 times more radioactive hyaluronic acid than the NF (P less than 0.001); molecular volume by gel chromatography was similar and suggested a high molecular weight product. SF were essentially as responsive to normal lymphoid and platelet factors as were NF. No consistent qualitative or quantitative differences in sulfated GAG synthesis were noted between the 2 groups of cells. Incubation of NF and SF with a false "core protein" such as p-nitrophenyl-beta-D-xyloside suggested that synthesis of the core protein was rate limiting; SF and NF were equally facile in SO4-GAG chain synthesis in the presence of a beta-xyloside. SF appear to retain in vitro a partially activated state for many generations, at least with respect to hyaluronic acid synthesis.