The characterisation and function of the polysaccharidases of human synovial fluid in rheumatoid and osteoarthritis.
A potential enzymic mechanism for the degradation of glycosaminogly cans was characterised using enzymes found in rheumatoid synovial fluid from the knee joint. This mechanism involves a true hyluronidase together with the concerted action of beta-glucuronidase and beta-N-acetylhexosaminidase. The contribution of the exopolysaccharidases to hyaluronate degradation was demonstrated by the use of specific inhibitors, while the distinct identity of a true hyaluronidase was shown by ammonium sulphate and agarose gel column fractionations. Only the hyluronidase fraction was capable of degrading high molecular weight hyaluronate. The exopolysaccharidase activities were shown to be markedly elevated in rheumatoid as compared to osteoarthritic synovial fluid and also normal serum. On the other hand, hyluronidase was similarly active in rheumatoid and osteoarthritic synovial fluids; both these levels were lower than that of normal human serum. Hyaluronidase in synovial fluid may thus be derived by diffusion from serum, since it is of relatively low molecular weight (60 000). The pH requirements of this enzyme system and the strong inhibition of hyaluronidase by synovial fluid make it unlikely that the mechanism operates extracellularly. It is proposed that as a lysosomal mechanism, however, it is an important contributing factor in the chronic erosion process characteristic of rheumatoid arthritis.
D000085:Acetates / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D005966:Glucuronidase / Q000378:metabolism*; D006025:Glycosaminoglycans; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008970:Molecular Weight; D010003:Osteoarthritis / Q000201:enzymology*; D012965:Sodium Chloride / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism*; D013997:Time Factors
D000085:Acetates; D006025:Glycosaminoglycans; D007783:Lactones; D012965:Sodium Chloride; D006596:Hexosaminidases; D005966:Glucuronidase; D006821:Hyaluronoglucosaminidase; D008274:Magnesium