Immune regulation of collagenase secretion in rheumatoid and osteoarthritic synovial cell cultures

Primary cultures of synovial cells were obtained by proteolytic dispersion of synovial tissue from patients with rheumatoid arthritis (n = 19), psoriatic arthritis (n = 2), osteoarthritis (n = 13) and other joint problems (n = 3). The levels of endogenously secreted collagenase were variable from patient to patient but did not differ significantly between rheumatoid arthritis and osteoarthritis. The endogenous collagenase secretion was likely a consequence of mononuclear cell factor (MCF) release from monocytes/macrophages which have been shown to be present among the heterogeneous primary rheumatoid synovial cell population (Dayer et al., 1976). As also demonstrated by these investigators, medium containing MCF can be generated from peripheral blood mononuclear cells in a T lymphocyte-dependent process by the addition of phytohemagglutinin (PHA). The addition of such medium stimulated collagenase secretion from all our synovial cell cultures regardless of the endogenous level. Protein synthesis but not synovial cell proliferation was required for MCF stimulation of collagenase secretion. The direct addition of PHA to primary synovial cell cultures stimulated collagenase secretion in some but not all cases indicating the presence of T lymphocytes in these positively-responding cultures. In some of these primary synovial cell cultures in which the addition of PHA stimulated collagenase secretion, secretion was also stimulated by the addition of collagen peptides, native collagen, proteoglycan or purified protein derivative of tuberculin. We propose that, in these instances, MCF release is mediated by antigen-sensitized lymphocytes. Antigen-responsive cultures were not restricted to the rheumatoid population. Our data are compatible with the idea that infiltrated lymphocytes in inflamed synovial tissue become sensitized to cartilage and joint capsule components released during tissue degradation and contribute to matrix destruction by mediating MCF release with consequent stimulation of collagenase synthesis and secretion from synovial cells.