The Elimination of α₂-Macroglobulin Complexes from the Arthritic Joint: An Experimental Study in Dogs

Abstract

The polyvalent protease inhibitor, α₂-macroglobulin, may counteract a protease-mediated rheumatoid joint destruction. The elimination of the complexed inhibitor from joints was analysed in inflamed and noninflamed conditions of the knee joints in dogs. The arthritis was immunologically induced. The fate of intraarticularly injected radioactive α₂-macroglobulin complexes was studied by external measurements, analyses of blood, lymph and urine, and by autoradiographic and immunohistologic methods. The results indicate that the elimination of complexes was accelerated by inflammation and joint movements with a half-life shorter than 2 hours in acute arthritis. In addition to absorption into the synovial membrane and degradation in macrophage-like cells, the process of clearance included elimination of complexes via the blood and the lymph capillaries of the joint and subsequent degradation in cells belonging to the reticuloendothelial system in the lymph nodes and the liver. The degradation products were excreted in increasing amounts in the urine. Referring to the earlier recognized high degree of saturation of synovial fluid α₂-macroglobulin in rheumatoid arthritis, the finding of a rapid articular clearance of α₂-macroglobulin complexes suggests a pronounced release of endoproteases under clinical conditions.