Stimulation of Plasmin Catalyzed Conversion of SingleChain to Two-Chain Urokinase-Type Plasminogen Activator by Sulfated Polysaccharides

Summary

Influence of heparin, chondroitin sulfate C and dextran sulfate (MW 3,500 and 7,000) on plasmin catalyzed conversion of singlechain (scu-PA) to two-chain (u-PA) urokinase-type plasminogen activator and generation of plasmin in mixtures of scu-PA and Glu-plasminogen (Glu-plg) was investigated. Conversion of scu-PA to u-PA catalyzed by plasmin was enhanced by chondroitin sulfate C and heparin, maximally by 10-fold and 3-fold, respectively. Sulfated polysaccharides potentiated generation of plasmin in mixtures of Glu-plg and scu-PA, as well as enhanced plasminogenolytic activity of u-PA. The possible role of these interactions is discussed.

Keywords

Single-chain urokinase-type plasminogen activator - Two-chain urokinase-type plasminogen activator - Sulfated polysaccharides - Potentiation

• References

• 1 Ungar G, Mist SH. Observations on the release of serum fibrinolysin by specific antigen, peptone and certain polysaccharides. J Exp Med 1949; 90: 39-51
• 2 Kaulla KN v, Me Donald TS. The effect of heparin on components of the human fibrinolytic system. Blood 1958; 13: 811-821
• 3 Rosa AT, Rotshild AM, Rotshild Z. Fibrinolytic activity evoked in plasma of the normal and adrenalectomized rat by cellulose sulphate. Br J Pharmacol 1972; 45: 470-475
• 4 Kumada T, Abiko Y. Fibrinolytic action of a new semi-synthetic polysaccharide sulfate, galactan polysulfate (DH 6322), in the rat. Thromb Res 1985; 39: 9-19
• 5 Vinazzer H, Stemberger A, Haas S, Blumel G. Influence of heparin of different heparin fractions and of a low molecular weight heparin-like substance on the mechanism of fibrinolysis. Thromb Res 1982; 27: 341-352
• 6 Klocking HP, Markwardt F. Release of plasminogen activator by pentosan polysulfate. Thromb Res 1986; 41: 739-744
• 7 Agnelli G, Borin J, Cosmi B, Levi M, ten Cate JW. Effects of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis. Thromb Haemostas 1988; 60: 311-313
• 8 Grimaudo V, Omri A, Kruithof EK O, Hauert J, Bachmann F. Fibrinolytic and anticoagulant activity after a single subcutaneous administration of heparin or a low molecular weight heparin-dihydroergotamine combination. Thromb Haemostas 1988; 59: 388-391
• 9 Klauser RJ. Induction of fibrinolysis by poly anions in human plasma. Thromb Haemostas 1988; 60: 324-327
• 10 Andrade-Gordon P, Strickland S. Interaction of heparin with plasminogen activators and plasminogen: effects on the activation of plasminogen. Biochemistry 1986; 25: 4033-4040
• 11 Paques EP, Stohr HA, Heimburger N. Study on the mechanism of action of heparin and related substances on the fibrinolytic system: relationship between plasminogen activators and heparin. Thromb Res 1986; 42: 797-807
• 12 Fears R. Kinetic studies on the effect of heparin on plasminogen activators. Biochem J 1988; 249: 77-81
• 13 Dosne AM, Bendetowicz AV, Kher A, Samama M. Marked potentiation of the plasminogenolytic activity of pro-urokinase by unfractionated heparin and a low molecular-weight heparin. Thromb Res 1988; 51: 627-630
• 14 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
• 15 Wohl RC, Summaria L, Robbins K. Kinetics of activation of human plasminogen by different activator species at pH 7.4 and 37° C. J Biol Chem 1980; 255: 2005-2013
• 16 Urano T, Sator de Serrano V, Gaffney PJ, Castellino FJ. The activation of human (Glu¹) plasminogen by human single-chain urokinase. Arch Biochem Biophys 1988; 264: 222-230
• 17 Lijnen HR, Collen D. Stimulation by heparin of the plasmin mediated conversion of single-chain to two-chain urokinase-type plasminogen activator. Thromb Res 1986; 43: 687-690
• 18 Kluft C. Studies on the fibrinolytic system in human plasma: Quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
• 19 Takada A, Takada Y. Plasminogen activators: possible role in cell proliferation. Dermatologica 1989. in press
• 20 Fukatsu T, Sobue M, Nagasaka T, Ohiwa N, Fukata S, Nakashima N, Takeuchi J. Immunohistochemical localization of chondroitin sulfate and dermatan sulphate in tumor tissues. Br J Cancer 1988; 57: 74-78
• 21 Gulba DC, Fischer K, Reil GH, Daniel WG, Lichtlen PR. Potentiation of the thrombolytic efficacy of single-chain urokinase (pro-urokinase) by heparin. Thromb Haemostas 1988; 60: 350-351
• 22 Fareed J, Kumar A, Walenga JM, Hoppensteadt D. Heparin and related mucopolysaccharide interactions with thrombolytic and profibrinolytic agents: pharmacologic studies in primates: Fibrinolysis. 1988; Suppl (Suppl. 01) 16 (Abstract)