Activation of Fibroblasts Induced by Mononuclear Cells from Patients with Systemic Scleroderma and Inactivation by Mitogen Stimulation

Abstract

Unstimulated mononuclear cell supernatants from patients with systemic scleroderma significantly augmented the DNA and collagen biosynthesis of 3T3 cells compared to normal mononuclear cells. This increase was suppressed by either a particular glycosaminoglycan, which from previous studies, has appeared to act as one of the tissue antigens in sclerotic skin, or concanavalin A stimulation.

Clinical Significance of Lymphocyte Responsiveness to Scleroderma-Inducing Glycosaminoglycan-Associated Antigen in Systemic Scleroderma

“…We had already found that peripheral lympho cytes ofSSD patients responded significantly to crude SI-GAG [6], In a further study, the initial SI-GAG was found to be composed of two active subsets: purified SI-GAG (an LNSHS, fraction A) and low-molecular frac tion (fraction C). Ofthese, the minor fraction (fraction C) stimulated mononuclear cells of patients with SSD significantly, but the puri fied SI-GAG did not [23]. Our current work revealed further that cells responsive to the minor subset were T cells [11], In the present study, a large number of SSD patients were examined, and patients with lymphocytes responding to the antigen associated with the SI-GAG are described.…”

“…The immune response to the urinary antigen may be unique in that the antigen is found to be associated with SI-GAG [6], and that both benign and severely involved patients, viewed from clinical and immunological features, reacted with the antigen, but at dif ferent levels, depending on the amount of in volvement. In our previous work, SSD lym phocytes that were significantly stimulated by this antigen inhibited synthetic activities of murine fibroblasts [11,23], whereas lym phocytes from patients with no response did not suppress the DNA synthesis of fibro blasts [11]. Therefore, a moderate response may presage a relatively benign course.…”

“…The sample was then applied to a Dowex 1-X2 column to elute GAG with NaCI solutions. The 0.8 M NaCI eluate was directly transferred into a Sephadex G-50 column and eluted with water, in order to sep arate the SI-GAG (fraction A), fraction B and the anti gen (fraction C)in the order ofelution [23], Details of the isolation procedure used in this study will be described in another report.…”