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Thromb Haemost 1995; 73(03): 472-477
DOI: 10.1055/s-0038-1653799
Original Articles
Fibrinolysis
Schattauer GmbH Stuttgart

Interactions of Staphylokinase with Human Platelets

H R Lijnen
The Center for Molecular and Vascular Biology, University of Leuven, Belgium
,
B Van Hoef
The Center for Molecular and Vascular Biology, University of Leuven, Belgium
,
D Collen
The Center for Molecular and Vascular Biology, University of Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Received07 July 1994

Accepted after resubmission 08 November 1994

Publication Date:
09 July 2018 (online)

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Summary

The interactions of recombinant staphylokinase (SakSTAR) with human platelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarction (AMI) treated with SakSTAR.

In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered by addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin- activated platelets was very low. ADP-induced or collagen-induced platelet aggregation in platelet-rich plasma (PRP) was 94 ± 2.7% or 101 ± 1.7% of control in the presence of 0.1 to 20 μM SakSTAR, with corresponding values of 95 ± 2.8% or 90 ± 4.6% of control in the presence of 0.1 to 4 μM SK. No effects were observed on platelet disaggregation. ATP secretion following collagen-induced platelet aggregation was 4.3 ± 0.26 μM for SakSTAR (at concentrations of 0.1 to 20 μM) and 4.4 ± 0.35 μM for SK (at concentrations of 0.1 to 4 μM), as compared to 3.4 ± 0.70 μM in the absence of plasminogen activator.

Fifty % lysis in 2 h (C50) of 60 μl 125I-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM SakSTAR and with 49 or 40 nM SK, respectively. C50 values for lysis of 60 μl PRP clots prepared from normal or patient plasma were also comparable for SakSTAR (19 or 21 nM), whereas SK was 2-fold more potent toward PRP clots prepared from Glanzmann plasma as compared to normal plasma (C50 of 130 versus 270 nM).

No significant effect of SakSTAR on platelet function was observed in plasma from patients with AMI treated with SakSTAR, as revealed by unaltered platelet count, platelet aggregation and ATP secretion.

Thus, no effects of high SakSTAR concentrations were observed on human platelets in vitro, nor of therapeutic SakSTAR concentrations on platelet function in plasma.

 

  • References

  • 1 Sakai M, Watanuki M, Matsuo O. Mechanism of fibrin-specific fibrinolysis by staphylokinase: participation of α2-plasmin inhibitor. Biochem Biophys Res Comm 1989; 162: 830-837
    CrossrefPubMedGoogle Scholar
  • 2 Matsuo O, Okada K, Fukao H, Tomioka Y, Ueshima S, Watanuki M, Sakai M. Thrombolytic properties of staphylokinase. Blood 1990; 76: 925-929
    PubMedGoogle Scholar
  • 3 Lijnen HR, Van Hoef B, De Cock F, Okada K, Ueshima S, Matsuo O, Collen D. On the mechanism of fibrin-specific plasminogen activation by staphylokinase. J Biol Chem 1991; 266: 11826-11832
    CrossrefPubMedGoogle Scholar
  • 4 Kowalska-Loth B, Zakrzewski K. The activation by staphylokinase of human plasminogen. Acta Biochim Pol 1975; 22: 327-339
    PubMedGoogle Scholar
  • 5 McClintock DK, Bell PH. The mechanism of activation of human plasminogen by streptokinase. Biochem Biophys Res Commun 1971; 43: 694-702
    CrossrefPubMedGoogle Scholar
  • 6 Collen D, Schlott B, Engelborghs Y, Van Hoef B, Hartmann M, Lijnen HR, Behnke D. On the mechanism of the activation of human plasminogen by recombinant staphylokinase. J Biol Chem 1993; 268: 8284-8289
    CrossrefPubMedGoogle Scholar
  • 7 Lijnen HR, Van Hoef B, Matsuo O, Collen D. On the molecular interactions between plasminogen-staphylokinase, α2-antiplasmin and fibrin. Biochim Biophys Acta 1992; 1118: 144-148
    CrossrefPubMedGoogle Scholar
  • 8 Silence K, Collen D, Lijnen HR. Regulation by α2-antiplasmin and fibrin of the activation of plasminogen with recombinant staphylokinase in plasma. Blood 1993; 82: 1175-1183
    PubMedGoogle Scholar
  • 9 Lijnen HR, Van Hoef B, Vandenbossche L, Collen D. Biochemical properties of natural and recombinant staphylokinase. Fibrinolysis 1992; 6: 214-225
    PubMedGoogle Scholar
  • 10 Collen D, De Cock F, Vanlinthout I, Declerck PJ, Lijnen HR, Stassen JM. Comparative thrombolytic and immunogenic properties of staphylokinase and streptokinase. Fibrinolysis 1992; 6: 232-242
    PubMedGoogle Scholar
  • 11 Collen D, De Cock F, Stassen JM. Comparative immunogenicity and thrombolytic properties towards arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons. Circulation 1993; 87: 996-1006
    CrossrefPubMedGoogle Scholar
  • 12 Collen D, Van de Werf F. Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction. Circulation 1993; 87: 1850-1853
    CrossrefPubMedGoogle Scholar
  • 13 Schlott B, Hartmann M, Gϋhrs KH, Birch-Hirschfeld E, Pohl HD, Vanderschueren S, Van de Werf F, Michoel A, Collen D, Behnke D. High yield production and purification of recombinant staphylokinase for thrombolytic therapy. BioTechnology 1994; 12: 185-189
    CrossrefPubMedGoogle Scholar
  • 14 Collen D, Silence K, Demarsin E, De Mol M, Lijnen HR. Isolation and characterization of natural and recombinant staphylokinase. Fibrinolysis 1992; 6: 203-213
    PubMedGoogle Scholar
  • 15 De Reys S, Hoylaerts MF, De Ley M, Vermylen J, Deckmyn H. Fc-independent crosslinking of a novel platelet membrane protein by a monoclonal antibody causes platelet activation. Blood 1994; 84: 547-555
    PubMedGoogle Scholar
  • 16 Marchalonis JJ. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem J 1969; 113: 299-305
    CrossrefPubMedGoogle Scholar
  • 17 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 18 Vaughan DE, Van Houtte E, Declerck PJ, Collen D. Streptokinase-induced platelet aggregation. Prevalence and mechanism Circulation 1991; 84: 84-91
    CrossrefPubMedGoogle Scholar
  • 19 Miles LA, Plow EF. Binding and activation of plasminogen on the platelet surface. J Biol Chem 1985; 260: 4304-4311
    PubMedGoogle Scholar
  • 20 The Gusto Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-682
    CrossrefPubMedGoogle Scholar
  • 21 Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JN, Collen D. Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis Circulaton 1989; 79: 920-928
    CrossrefPubMedGoogle Scholar
  • 22 Gold HK, Coller BS, Yasuda T, Saito T, Fallon JT, Guerrero JL, Leinbach RC, Ziskind AA, Collen D. Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation. Circulation 1988; 77: 670-677
    CrossrefPubMedGoogle Scholar
  • 23 Sabovic M, Lijnen HR, Keber D, Collen D. Effect of retraction on the lysis of human clots with fibrin specific and non-fibrin specific plasminogen activators. Thromb Haemost 1989; 62: 1083-1087
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Sobel BE, Nachowiak DA, Fry ET A, Bergmann SR, Torr SR. Paradoxical attenuation of fibrinolysis attributable to “plasminogen steal” and its implications for coronary thrombolysis. Coron Art Dis 1990; 1: 111-119
    CrossrefPubMedGoogle Scholar
  • 25 Suehiro A, Oura Y, Ueda M, Kakishita E. Inhibitory effect of staphylokinase on platelet aggregation. Thromb Haemost 1993; 70: 834-837
    Article in Thieme ConnectPubMedGoogle Scholar