A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)
article
Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA) for the assessment of tcu-PA/T in human body fluids. In this BIA, urokinase antigen was immuno-immobilized in microtiter plates and treated with cathepsin C, a specific activator of tcu-PA/T, after which plasminogen activator activity was measured. The occurrence of tcu-PA/T was assessed in the plasma of healthy individuals and sepsis patients, and in the synovial fluid of rheumatoid arthritis patients. In addition, the concentrations of urokinase antigen and scu-PA were measured. In the plasma of the healthy individuals the concentration of tcu-PA/T was below the detection limit of 0.2 ng/ml. In the plasma of almost all sepsis patients tcu-PA/T was found (median value 0.4 ng/ml). In the synovial fluid of all rheumatoid arthritis patients tcu-PA/T could be measured (median value 5.4 ng/ml), and its concentration was about twofold higher than the concentration found for scu-PA. In this group tcu-PA/T contributed to about 47% (median value) of urokinase antigen. From these data we conclude that inactivation of scu-PA by thrombin can take place in vivo under pathological conditions which involve the production of thrombin. In this way thrombin may regulate fibrinolysis and extracellular proteolysis.
TNO Identifier
233657
ISSN
02689499
Source
Fibrinolysis, 10(SUPPL. 3), pp. 95.
Article nr.
Abstract 320
Pages
95
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