Functionally active α2-macroglobulin and kinin release in synovial fluids of rheumatoid arthritis
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The function of α2M (α2-macroglobulin) as a proteinase inhibitor in synovial fluid of rheumatoid arthritis was investigated. Low esterase activity was found in the 19S sieve fraction of Sephadex G-200 gel filtered synovial fluid samples, comparable with that obtained with normal human plasma. The molar binding ratio of α2M isolated from the synovial fluid and trypsin was estimated according to earlier established methods. The formation of an equimolar complex indicated that the synovial α2M was functionally intact.
Esterase activities were measured on αN-tosyl-l-arginine [3H]methyl ester. Synovial fluid samples were all found to contain proteinase enzyme which did not bind to the synovial α2M nor to the added functionally intact, immunologically pure α2M prepared from normal human plasma.
Albumin, α1-acid glycoprotein, α2HS-glycoprotein, α2M and kininogen in synovial fluids were determined by single radial immunodiffusion. Only the α2M contents were clearly lower than in normal human serum per ml.
The higher than 1 ratio between the immunoreactive kininogen determined with monospecific anti-human kininogen serum and the pharmacologically active kininogen indicated that kinin release had occurred possibly in the synovial membrane. Proteinase enzymes present in the synovial fluids and unbound to α2M caused further depletion of the active kinin segment in synovial kininogen. A model of the regulation by α2M of the synovial kininogen-kinin system is given.
KeywordsRheumatoid Arthritis Synovial Fluid Esterase Activity Binding Ratio Normal Human Serum
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