Products of activated mononuclear cells modulate accumulation of collagen by normal dermal and scleroderma fibroblasts in culture

Abstract

Supernatants of human mononuclear cells activated with concanavalin A contain soluble factors that modulate accumulation of collagen in human dermal fibroblasts in culture. The supernatants decreased collagen accumulation by 67% in normal fibroblast lines and by greater than 80% in lines established from skin of patients with scleroderma. Collagen was measured by incorporation of 3H-proline into collagenase-sensitive protein. The inhibitory activity of collagen was optimal after a 24-hour incubation of confluent fibroblast monolayers with unfractionated mononuclear cell supernatants. Kinetic studies of this response showed a delay in accumulation of collagen-sensitive protein in supernatant-treated cultures. The 3H-thymidine uptake and fibroblast cell count and viability were only minimally altered. Noncollagen protein was inhibited by 30% to 40%. The presence of serum in fibroblast cultures did not affect this activity. The inhibitory factors were produced by purified T-lymphocyte subpopulations. Supernatant inhibitory activity was present after removal of monocytes from mononuclear cell cultures. By gel filtration on Sephadex G-100, active supernatants fractionated into at least three peaks of activity with molecular weight of 50,000, 30,000, and 15,000 daltons. Interleukin 1 might be one of the factors in mononuclear cell supernatants that modulates production of collagenase-sensitive protein in human dermal fibroblasts. Factors modulating collagen-sensitive protein are important in processes leading to excessive accumulation of the connective tissue and fibrosis in certain diseases.