| Popis: |
Deposition of fibrin-like material on the synovival membrane of inflamed joints is a prominent and persistent feature of RA. To evaluate the involvement of the classical coagulation cascade in the formation of this material, fibrinopeptide A (FPA) and coagulation factors were analyzed in synovial fluid from RA patients. FPA was 1100 ng/ml (range 300-3200; n=l6), compared to 200 ng/ml (60-300;n=13) in synovial fluid from patients with osteoarthritis. No significant change (p> 0.2; n=l4) in FPA immunoreactivity (using R2 anti-FPA serum from Dr Nossel beside the antiserum from our institute) was observed after thrombin treatment of the diffusate of dialyzed synovial fluids. This finding indicates that the high levels of FPA immunoreactivity in joint fluids of RA reflect FPA (Aα 1-16) instead of FPA-like fibrinogen fragments (which can be cleaved from fibrinogen by e.g. granulocytic proteases). In view of the finding that all coagulation factors including fibrinogen were sufficiently present (30-100%; n=l8) - except FV (To investigate the mechanisms of this activation, normal plasma was incubated with human articular cartilage and activation of FXII was determined by measuring the generation of bradykinin (radioimmunoassay). Cartilage activated FXII whereas its activation capacity was strongly enhanced by pre-exposition to granulocytic enzymes (compare in vivo!). Among its constituents collagen (type II) activated FXII, but proteoglycans were only weak activators. Both substances were isolated from human cartilage, obtained from a normal knee joint at necropsy. With respect to the contribution of the extrinsic coagulation pathway it was shown that synovial fluids from RA patients stimulated the thromboplastin generation by normal human monocytes. Taken together, these findings suggest that both intrinsic and extrinsic coagulation pathways, presumably triggered by the inflammatory process itself, are involved in articular fibrin deposition. |
