Generation of kinins in synovial fluid from patients with arthropathy.
An enzyme-linked immunosorbent assay method is described for the measurement of kinin formation in synovial fluid from patients with rheumatoid and osteoarthritis (RA and OA). Basal kinin concentrations were less than 6 ng/ml in synovial fluid collected in the presence of inhibitors of kinin forming (kininogenase) and kinin metabolising (kininase) enzymes. During incubation of synovial fluid in the presence of kininase inhibitors alone, kinins were produced rapidly over the first 10 min, but production ceased completely within 30 min due to inhibition of the endogenous kininogenases; the rate of kinin generation during the early rapid phase correlated well with the plateau kinin concentration. Plateau kinin levels in synovial fluid from 15 patients with OA and RA ranged from 98 to 427 ng/ml, with a median value of 148 ng/ml. This study demonstrates clearly that synovial fluid from arthritis patients has the capacity to produce kinins. Although the number of patients was small, the amount of kinin generated in vitro varied over a wide range and a relationship between intra-articular kinin formation and clinical features may become apparent in a larger group of patients. The technique could also be used to investigate other biological systems in which a role has been proposed for kinins.
Bond
A P
AP
Department of Pharmacology, University of Bristol, UK.
Lemon
M
M
Dieppe
P A
PA
Bhoola
K D
KD
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D001667:Binding, Competitive; D001920:Bradykinin / Q000032:analysis / Q000096:biosynthesis; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002356:Cartilage / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D007609:Kallidin / Q000032:analysis / Q000096:biosynthesis; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000032:analysis / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism*
D003574:Cytochrome c Group; D007704:Kininogens; D007705:Kinins; D007609:Kallidin; D006821:Hyaluronoglucosaminidase; D002268:Carboxypeptidases; D007610:Kallikreins; D001920:Bradykinin