Macrophage-fibroblast interactions in collagenase production and cartilage degradation

Abstract

Rabbit bone-marrow macrophages and fibroblasts were cultured, independently or together, with pieces of 35S-labelled cartilage or at the surface of dried [14C]collagen gels. Each type of cell, cultivated alone, rapidly degraded the proteoglycan of cartilage, but only the fibroblasts degraded collagen. The co-culture of both types of cell had no consistent effect on the rate of proteoglycan degradation, but it stimulated the rate of collagen degradation. In parallel, the accumulation of collagenase in the culture fluid was enhanced but not that of neutral proteinase. Coinditioned media from macrophage cultures added to cultures of fibroblasts had the same effect as the living macrophages in stimulating the production of collagenase. Their action was itself enhanced when the macrophages had been activated by concanavalin A-stimulated spleen-cell factors. These data suggest that fibroblasts may act as effector cells in producing collagenase and degrading collagen in response to soluble factors released by macrophages under the control of lymphocyte factors.

Degradation of heparan sulfate in the subendothelial extracellular matrix by a readily released heparanase from human neutrophils. Possible role in invasion through basement membranes.

“…The present results with neutrophils, and our previous studies with lymphocytes (18,19) and macrophages (18), suggest a mechanism for modulation of heparanase activity and release in response to various signals. On the other hand, blood-borne tumor cells either may exhibit a constitutive expression of the enzyme in correlation with their metastatic potential (16,17) or can recruit normal cells (macrophages, neutrophils, lymphocytes, and platelets) and capitalize on their ability to infiltrate tissues (40,41).…”

Human mononuclear cell factors mediate cartilage matrix degradation through chondrocyte activation.

“…These authors showed that although matrix degradation took place in cultures of synovium over-lapping with dead cartilage, optimal proteoglyean release required interaction of living synovium with live cartilage. A related group of investigations have dealt with factors secreted by mononuclear cells that induce secretion of collagenase and neutral proteases from chondrocytes (7)(8)(9), rheumatoid synovial cells (10), fibroblasts (11), and macrophages (12) in culture. It was postulated that the increased production of these enzymes in vivo may mediate cartilage degradation, but there has been no direct evidence that connective tissue cells stimulated by such factors are able to mediate matrix degradation in living cartilage.…”

Macrophages stimulate the activation of plasminogen by fibroblasts

“…Thus rabbit macrophage factor(s) or monokine(s) appear to be able to stimulate the release or the activity of several neutral proteases active in collagen and proteoglycan degradation by rabbit libroblasts [4,5], chondrocytes [15] or synovial cells [5]. Similarly, a human mononuclear cell factor has been shown to stimulate collagenase [ 161 or plasminogen activator [17] production by human synovial cells and a human synovial cell factor (possibly released by the macrophage-like, type-A synovial lining cells, as discussed in [3]) stimulates the activation of plasminogen by human chondrocytes [IS].…”

“…Macrophage-conditioned media were obtained by culturing [4,7] adherent macrophages for 6 days at 37°C in plastic Petri dishes in basal medium supplemented with 10 mM-HEPES and 5% acidtreated FCS at a density of 5 x lo5 cells/ml (about 8 X 104 cells/cm2). The conditioned medium was then centrifuged and stored at -20°C until use.…”

“…Macrophages and libroblasts are among the main effector cells in these processes and they have been shown to be able to cooperate both in tissue growth and librogenesis [ 1,2] and in the degradation of connective tissue matrices [3]. We have shown previously that macrophages release a factor that stimulates the production of collagenase and of a proteoglycandegrading neutral protease by rabbit skin fibroblasts or by adherent synovial cells and that this production can itself be modulated by lymphocyte products [4,5]. We now report here that macrophages may also stimulate skin fibroblasts to activate plasminogen.…”