Lymphocyte-macrophage-fibroblast co-operation in the inflammatory degradation of cartilage and connective tissue.

In tissue culture models of cartilage and connective tissue degradation, rabbit macrophages and fibroblasts are both independently capable to degrade cartilage proteoglycan due to the secretion of a metal-dependent neutral proteinase. However, only the fibroblasts significantly degrade the collagen due to a sufficient production of collagenase. Macrophages produce factor(s) that stimulate the secretion of collagenase and the degradation of collagen by fibroblasts. Soluble products released by stimulated lymphocytes increase that production and also markedly enhance the secretion of proteoglycan-degrading proteinase and of collagenase by the macrophages. These data support the view that macrophages and fibroblasts are among the main effector cells of cartilage degradation in rheumatoid arthritis and that they are regulated in this function by secretory products of nearby lymphocytes.