Streptokinase-induced platelet activation involves antistreptokinase antibodies and cleavage of protease-activated receptor-1

Blood. 2000 Feb 15;95(4):1301-8.


Streptokinase activates platelets, limiting its effectiveness as a thrombolytic agent. The role of antistreptokinase antibodies and proteases in streptokinase-induced platelet activation was investigated. Streptokinase induced localization of human IgG to the platelet surface, platelet aggregation, and thromboxane A(2) production. These effects were inhibited by a monoclonal antibody to the platelet Fc receptor, IV.3. The platelet response to streptokinase was also blocked by an antibody directed against the cleavage site of the platelet thrombin receptor, protease-activated receptor-1 (PAR-1), but not by hirudin or an active site thrombin inhibitor, Ro46-6240. In plasma depleted of plasminogen, exogenous wild-type plasminogen, but not an inactive mutant protein, S(741)A plasminogen, supported platelet aggregation, suggesting that the protease cleaving PAR-1 was streptokinase-plasminogen. Streptokinase-plasminogen cleaved a synthetic peptide corresponding to PAR-1, resulting in generation of PAR-1 tethered ligand sequence and selectively reduced binding of a cleavage-sensitive PAR-1 antibody in intact cells. A combination of streptokinase, plasminogen, and antistreptokinase antibodies activated human erythroleukemic cells and was inhibited by pretreatment with IV.3 or pretreating the cells with the PAR-1 agonist SFLLRN, suggesting Fc receptor and PAR-1 interactions are necessary for cell activation in this system also. Streptokinase-induced platelet activation is dependent on both antistreptokinase-Fc receptor interactions and cleavage of PAR-1. (Blood. 2000;95:1301-1308)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Amino Acid Sequence
  • Antibodies / pharmacology
  • Antibodies, Bacterial / pharmacology
  • Antibodies, Bacterial / physiology*
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Calcium / metabolism
  • Hirudins / pharmacology
  • Humans
  • In Vitro Techniques
  • Leukemia, Erythroblastic, Acute
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Platelet Activation / drug effects
  • Platelet Activation / physiology*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / physiology*
  • Receptor, PAR-1
  • Receptors, Fc / physiology*
  • Receptors, Thrombin / immunology
  • Receptors, Thrombin / physiology*
  • Streptokinase / immunology
  • Streptokinase / pharmacology*
  • Tumor Cells, Cultured


  • Antibodies
  • Antibodies, Bacterial
  • Hirudins
  • Peptide Fragments
  • Receptor, PAR-1
  • Receptors, Fc
  • Receptors, Thrombin
  • Adenosine Diphosphate
  • Streptokinase
  • Calcium