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Endogenous platelet fibrinogen surface expression on activated platelets.

H R Gralnick1, S Williams, L McKeown

  • 1Hematology Service, Clinical Center, National Institutes of Health, Bethesda, MD 20892.

The Journal of Laboratory and Clinical Medicine
|December 1, 1991
PubMed
Summary
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Platelet fibrinogen surface expression is primarily mediated by release and binding to the glycoprotein IIb-IIIa complex, with some prebound or alternative receptor binding also observed.

Area of Science:

  • Hematology
  • Platelet Biology
  • Molecular Biology

Background:

  • Platelet fibrinogen is stored in alpha-granules and derived from megakaryocyte endocytosis of plasma fibrinogen.
  • Surface expression of platelet fibrinogen is a key aspect of platelet function.

Purpose of the Study:

  • To investigate the mechanisms of intracellular platelet fibrinogen surface expression.
  • To determine the role of the glycoprotein IIb-IIIa (GPIIb-IIIa) complex in this process.

Main Methods:

  • Utilized murine monoclonal antibody fragments (F26) and polyclonal antifibrinogen antibodies to study surface expression.
  • Investigated the effects of ethylene glycol tetraacetic acid (EGTA), calcium, Arg-Gly-Asp-Ser peptides, fibrinogen gamma-chain peptides, and antibody 10E5 on platelet fibrinogen expression.

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Main Results:

  • Platelet fibrinogen surface expression is proportional to GPIIb-IIIa complex expression in the presence of calcium.
  • Inhibition of GPIIb-IIIa complex before thrombin stimulation significantly reduced platelet fibrinogen expression (65-94%).
  • Inhibition was less effective when applied after thrombin stimulation or in washed platelets, suggesting release and binding are major mechanisms.

Conclusions:

  • The primary mechanism for platelet fibrinogen surface expression involves release and subsequent binding to the GPIIb-IIIa complex.
  • This binding can occur within the open canalicular system or on the platelet surface.
  • A smaller fraction (10-30%) may involve prebound fibrinogen or binding to alternative receptors.