Streptococcal cell walls and synovial cell activation. Stimulation of synovial fibroblast plasminogen activator activity by monocytes treated with group A streptococcal cell wall sonicates and muramyl dipeptide.

Abstract

Group A streptococcal peptidoglycan has previously been shown to be arthritogenic in rats and has been implicated as a structure present in a class of possible etiologic agents for rheumatoid arthritis. The present study reports that conditioned medium from human monocytes, after interaction with cell wall sonicates of four group A streptococcal strains, stimulates the plasminogen activator (PA) activity of nonrheumatoid synovial fibroblasts. Low concentrations of N-acetylmuramyl-L-alanyl-D isoglutamine (muramyl dipeptide) can also generate this synovial activator (SA) activity from human monocytes. Preliminary biochemical data suggest that the SA activity is distinct from interferon-gamma, interleukin 1, and interleukin 2. These results indicate that agents that are arthritogenic in rats can modulate human synovial fibroblast functions via monocytes. The findings are proposed to have possible significance for an understanding of the cellular interactions involved in the formation and function of the rheumatoid pannus, because PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation.

Interleukin‐1β and interleukin‐1α stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells

“…Synovial membrane tissue was obtained aseptically from the knees of patients who were known to be free of RA or degenerative joint disease, but who needed meniscectomy or other procedures to correct internal derangements. The techniques used for the culture and passage of cells from explant tissue were as previously described (2,4). The passaged cells were morphologically and biochemically similar to ' 'fibroblast-like" cells (2,4).…”

“…Several such studies have shown that polypeptide(s) (monokine [s]) from stimulated monocytes causes synoviocytes and chondrocytes to produce putative mediators of inflammation and matrix destruction, e.g., proteinases and prostanoids (1)(2)(3). A monokine(s), for example, elevates the levels of a serine proteinase, plasminogen activator (PA), in human synovial fibroblast-like cells (2,4). PA, which cleaves plasminogen to generate the less specific proteinase, plasmin, has been found to be elevated in rheumatoid arthritis (RA) synovial fluid (5) and to be present in RA tissue (6).…”

“…Monokine(s) can elicit several changes in synovial cells (1,2,4,(8)(9)(10)(11). In order to establish whether these changes are caused by the same molecule or by more than one, the use of defined monokines is required; however, because the levels of monokine(s) produced during cell culture are very low, purification and characterization of these proteins is difficult.…”

Stimulation of the hyaluronic acid levels of human synovial fibroblasts by recombinant human tumor necrosis factor α, tumor necrosis factor β (lymphotoxin), interleukin‐1α, and interleukin‐1β

“…Synovial membrane tissue was obtained aseptically from the knees of nonrheumatoid patients, i.e., patients who were free of disease but who needed correction of internal derangements, or who had degenerative joint disease. The synovial tissue was cultured using the explant technique (2,15). The passaged cells were morphologically and biochemically similar to fibroblast-like cells (2).…”

Human synovial fibroblasts produce urokinase‐type plasminogen activator

“…Synovial membrane tissue was obtained aseptically, as previously described (4, 11,12), from the knees of patients who were free of known rheumatoid or degenerative joint disease, but who needed correction of internal derangements, for example, by means of meniscectomy. The passaged cells thus obtained were morphologically and biochemically similar to "fibroblast-like" cells (4, 11,12).…”