RSS-Feed abonnieren
DOI: 10.1055/s-0038-1657120
Comparative Study of the Activity of High and Low Molecular Weight Urokinase in the Presence of Fibrin
Publikationsverlauf
Received 19. August 1981
Accepted 16. Dezember 1981
Publikationsdatum:
13. Juli 2018 (online)

Summary
The fibrinolytic or thrombolytic activity of low molecular weight urokinase (LMW-UK) and high molecular weight urokinase (HMW-UK) is not significantly different when measured in a bovine fibrin plate method, in a circulating plasma system containing a 125I-labelled human fibrin clot, or on 125I-fibrin films in culture plates using normal or α2-antiplasmin depleted human plasma.
In a human fibrin plate method however HMW-UK was found to be more active than LMW-UK. In a purified system on human 125I-fibrin films the activation of native or modified human plasminogen by HMW-UK was also found to be more effective than by LMW-UK.
Using a clot lysis test system we did not observe a different inhibition of LMW-UK and HMW-UK upon incubation in human plasma. This is in contrast with previous reports that HMW-UK is inhibited more rapidly in human plasma than LMW-UK.
In a purified system the inhibition rate of LMW-UK and HMW-UK by α2-antiplasmin is the same (rate constants at 25ΰC of 167 ± 9 M−1s−1 and 171 ± 5 M−1s−1 respectively).
The clinical trials available at present used doses of urokinase which were in excess of those required to obtain a maximal fibrinolytic effect. This might explain why in these trials no difference was observed between the thrombolytic effect of LMW-UK and HMW-UK, while in vitro HMW-UK appeared to be more effective. However, one should always be careful to extrapolate in vitro observations as such to the in vivo situation encountered during thrombolytic therapy.
-
References
- 1 Lormeau JC, Goulay J, Vairel EG, Choay J. A comment on the activities of high and low molecular weight urokinase. In: Fibrinolysis. Current Fundamental and Clinical Concepts. Gaffney PJ, Balkuv-Ulutin S. (Eds). 1978: 77-82 Academic Press; London:
- 2 Samama M, Cazenave B, Otero AM. Urokinase I and II activity. Thromb Haemostas 1978; 40: 578-580
- 3 Urokinase Pulmonary Embolism Trial. A national cooperative study. American Heart Association Monograph No 39. Circulation 1973; 47: 1-108
- 4 Urokinase-Streptokinase Pulmonary Embolism Trial. Phase 2, Results. A cooperative study. J Am Med Assoc 1974; 229: 1606-1613
- 5 Marder VJ, Donahoe JF, Bell WR, Cranley JJ, Kwaan HC, Sasahara AA, Barlow GH. Changes in the plasma fibrinolytic system during urokinase therapy: comparison of tissue culture urokinase with urinary source urokinase in patients with pulmonary embolism. J Lab Clin Med 1978; 92: 721-729
- 6 Murano G, Aronson DL. High and low molecular weight urokinase. Thromb Haemostas 1979; 42: 1066-1068
- 7 Murano G, Aronson D, Williams L, Brown L. The inhibition of high and low molecular weight urokinase in plasma. Blood 1980; 55: 430-436
- 8 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
- 9 Claeys H, Vermylen J. Physicochemical and proenzyme properties of NH2-terminal glutamic acid and NH2-terminal lysine human plasminogen. Influence of 6-aminohexanoic acid. Biochim Biophys Acta 1974; 342: 351-359
- 10 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Ark Kemi 1956; 10: 415-443
- 11 Wiman B. Affinity-chromatographic purification of human α2-antiplasmin. Biochem J 1980; 191: 229-232
- 12 Fenton II JW, Fasco MJ, Stackrow AB, Aronson DL, Young AM, Finlayson JS. Human thrombins. Production, evaluation, and properties of α-thrombin. J Biol Chem 1977; 252: 3587-3598
- 13 Wiman B, Collen D. On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem 1978; 84: 573-578
- 14 Edy J, De Cock F, Collen D. Inhibition of plasmin by normal and antiplasmin depleted human plasma. Thrombos Res 1976; 8: 513-518
- 15 Astrup T, Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch Biochem Biophys 1952; 40: 346-351
- 16 Hoylaerts M, Lijnen HR, Collen D. Studies on the mechanism of the antifibrinolytic action of tranexamic acid. Biochim Biophys Acta 1981; 673: 75-85
- 17 Matsuo O, Rijken DC, Collen D. Comparison of the relative fibrinogenolytic, fibrinolytic and thrombolytic properties of tissue plasminogen activator and urokinase in vitro. Thromb Haemostas 1981; 45: 225-229
- 18 Vermylen C, De Vreker R, Verstraete M. A rapid enzymatic method for assay of fibrinogen: the fibrin polymerization time (FPT-test). Clin Chim Acta 1963; 8: 418-424
- 19 Friberger P, Knös M. Plasminogen determination in human plasma. In: Chromogenic Peptide Substrates. Scully MF, Kakkar VV. (Eds). 128-140 Churchill Livingstone; Edinburgh: 1979
- 20 Suyama T, Nishida M, Iga Y, Naito R. Difference in thrombolytic effect between higher and lower molecular weight forms of urokinase. Thromb Haemostas 1977; 38: 48 (Abstr)
- 21 Philo RD, Gaffney PJ. Assay methodology for urokinase: its use in assessing the composition of mixtures of high- and low-molecular weight urokinase. Thromb Res 1981; 21: 81-88
- 22 Nobuhara M, Sakamaki M, Ohnishi H, Suzuki Y. A comparative study of high molecular weight urokinase and low molecular weight urokinase. J Biochem 1981; 90: 225-232
- 23 Ogston D, Bennett B, Herbert RJ, Douglas AS. The inhibition of urokinase by α2-macroglobulin. Clin Sci 1973; 44: 73-79
- 24 Clemmensen I, Christensen F. Inhibition of urokinase by complex formation with human alpha-1-antitrypsin. Biochim Biophys Acta 1976; 429: 591-599
- 25 Clemmensen I. Inhibition of urokinase by complex formation with human antithrombin III in absence and presence of heparin. Thromb Haemostas 1978; 39: 616-623
- 26 Moroi M, Aoki N. Isolation and characterization of α2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis. J Biol Chem 1976; 251: 5956-5965
- 27 Matsuo O, Kosugi T, Mihara H. Urokinase inactivation rate in the rabbit: effect of circulatory isolation of the liver, spleen and kidneys. Haemostasis 1978; 7: 367-372
- 28 Barlow GH, Marder VJ. Determination of plasma urokinase levels by chromogenic assay: comparison of levels attained during infusion of tissue culture and urinary source urokinase preparations. Thromb Haemostas 1979; 42: 295 (Abstr)
- 29 Barlow GH, Francis CW, Marder VJ. On the conversion of high molecular weight urokinase to the low molecular weight form. Thromb Haemostas 1981; 46: 11 (Abstr)