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Tissue factor regulates plasminogen binding and activation

Z Fan1, P J Larson, J Bognacki

  • 1Department of Pathology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Blood
|April 16, 1998
PubMed
Summary
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Tissue factor (TF) binds plasminogen, enhancing its activation and inhibiting fibrinolysis. This interaction, mediated by TF

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Tissue factor (TF) is crucial in hemostasis and thrombosis.
  • TF and plasminogen activators share roles in processes like atherogenesis and angiogenesis.
  • Interactions between TF and the plasminogen activator system are not fully understood.

Purpose of the Study:

  • To investigate the interaction between tissue factor (TF) and the plasminogen activator system.
  • To determine if plasminogen binds to TF and if TF modulates plasminogen activation.

Main Methods:

  • Optical biosensor interaction analysis to detect plasminogen binding to TF apoprotein.
  • Cell-based assays using Chinese hamster ovary (CHO) cells expressing TF.
  • Examination of plasmin formation via SDS-PAGE.

Related Experiment Videos

  • Inhibition assays for fibrinolysis and plasminogen binding.
  • Main Results:

    • Plasminogen directly binds to the extracellular domain of TF apoprotein via its kringle 1-3 domains.
    • TF expression on cells significantly increases plasminogen binding.
    • TF enhances urokinase-type plasminogen activator (uPA)-mediated plasminogen activation.
    • TF inhibits fibrinolysis and plasminogen binding to endothelial cells and trophoblasts.
    • TF and plasminogen colocalize in atherosclerotic plaques.

    Conclusions:

    • A high-affinity interaction exists between TF and plasminogen, mediated by TF's extracellular domain and plasminogen's kringle 1-3 regions.
    • TF modulates plasminogen localization and activation at extravascular sites.
    • This interaction has implications for TF's role in atherogenesis and other TF-mediated processes.