ABSTRACT
Collagen and proteoglycan are major constituents of the articular cartilage. In rheumatic disorders joint damage is attributed to the excessive action of proteoglycan degrading proteinases (P) and specific collagenases, which are released by connective tissue- and inflammatory cells in the synovial compartment. Collagenase is secreted in a latent form, which requires activation by a variety of serine-proteinases. Thus, several different proteinases are involved in pathogenesis of joint disease. alpha 2-macroglobulin was shown to be the major inhibitor of proteinases in complex biological fluids. To assess the utilization of alpha 2M by proteinases in synovial fluids (SF) from different arthritides we have employed a newly introduced solid phase immuno-sorbent assay, which allows concentration of alpha 2M and its proteinase-complexes from biological fluids. Most pronounced utilization of alpha 2M (up to 50% of total SF alpha 2M) was found in marked joint inflammation as judged from RF, immunocomplexes, C3 complement activation and acute phase reactants. Supported by animal experiments, which revealed that alpha 2M.P complexes but not native alpha 2M induce synovitis in rabbits after repeated intra-articular administration, it is suggested that pathophysiological rise of alpha 2M.P may impair cellular functions in inflammatory connective tissue, e.g. synovial tissue.
