Carboxypeptidase N (kininase I) activity in blood and synovial fluid from patients with arthritis.
Carboxypeptidase N (CPN, kininase I) and kininase II (angiotensin converting enzyme) activities were measured simultaneously in blood plasma and synovial fluid in patients suffering from rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA) and in the plasma of normal volunteers. CPN levels (defined as the rate of hydrolysis of furylacryloyl-Ala-Lys) in blood were modestly increased and correlated with erythrocyte sedimentation rate in RA and PA. Based on the hydrolysis of synthetic substrates, CPN activity was much higher than kininase II activity in synovial fluid (SF). SF kininase activities were always inferior to the blood levels in all patients and were correlated with the logarithm of SF leukocyte counts, an indicator of the intensity of inflammation. In addition, CPN and albumin levels in SF were highly correlated when expressed as a percent of the plasma concentrations. Biochemical properties of CPN in crude SF confirmed its similarity to blood CPN. Polymorphonuclear leukocytes derived from inflammatory SF did not release CPN. It is concluded that kininases diffuse from the blood into SF through increased vascular permeability and that CPN could be a major metabolic pathway for kinins in this form of exudate. CPN leads to the formation of des-Arg kinins, selective agonists of the B1 receptors for kinins.
D001168:Arthritis / Q000097:blood / Q000201:enzymology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000201:enzymology; D002268:Carboxypeptidases / Q000378:metabolism*; D006073:Gout / Q000097:blood / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D001121:Lysine Carboxypeptidase / Q000097:blood / Q000378:metabolism*; D010003:Osteoarthritis / Q000097:blood / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D011565:Psoriasis / Q000097:blood / Q000201:enzymology; D013582:Synovial Fluid / Q000201:enzymology*
D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase