High shear stress attenuates agonist-induced, glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked

Kaori Iijima, Mitsuru Murata, Kosei Nakamura, Tetsuya Kitaguchi, Makoto Handa, Kiyoaki Watanabe, Yoshihiro Fujimura, Akira Yoshioka, Yasuo Ikeda

Research output: Contribution to journalArticle

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Abstract

High shear stress facilitates von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib/IX, causing activation of GPIIb/IIIa to induce platelet aggregation. Here we report that activated GPIIb/IIIa, even occupied by ligands, is not sufficient to mediate platelet aggregation under high shear stress conditions when vWF binding to GPIb/IX is blocked. Platelet rich plasma or washed platelet suspension supplemented with purified human fibrinogen at a concentration of 2 mg/mL were treated with an anti-vWF monoclonal antibody NMC-4 which blocks the binding of vWF to GPIb/IX. After addition of 10 μmol/L ADP, aggregation was continuously monitored under various shear stress conditions (0-108 dyne/cm2) using a cone-plate type aggregometer previously described. The extent of maximal aggregation of agonist-stimulated platelets in the presence of NMC-4 correlated inversely with the level of shear stress applied, with the virtual absence of aggregation at 108 dyne/cm2. Once aggregated by 10 μmol/L ADP under low shear stress (12 dyne/cm2), platelets could be disaggregated, in part, by the application of high shear stress (108 dyne/cm2), and reaggregated when shear stress was returned to 12 dyne/cm2. Flow cytometric analysis revealed that platelets stimulated with 10 μmol/L ADP at 108 dyne/cm2 bound fluorescein isothiocyanate (FITC)-labeled fibrinogen, although aggregation was absent in this experimental condition. These results demonstrate the dual effect of shear stress on platelet functions; a pro-aggregating activity that induces vWF-GPIb/IX interaction leading to platelet activation, and an anti-aggregating force to prevent the growth of platelet thrombi. It is suggested that the efficacy of vWF blockade is greater under high shear than low shear stress conditions, and that a selective inhibition of platelet functions can be possible.

Original languageEnglish
Pages (from-to)796-800
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume233
Issue number3
DOIs
Publication statusPublished - 1997 Apr 28

Fingerprint

Platelet Glycoprotein GPIb-IX Complex
Platelet Glycoprotein GPIIb-IIIa Complex
von Willebrand Factor
Platelets
Platelet Aggregation
Shear stress
Blood Platelets
Agglomeration
Adenosine Diphosphate
Fibrinogen
Factor IX
Platelet-Rich Plasma
Platelet Activation
Fluorescein
Chemical activation
Platelet Membrane Glycoproteins
Suspensions
Thrombosis
Monoclonal Antibodies
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

High shear stress attenuates agonist-induced, glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked. / Iijima, Kaori; Murata, Mitsuru; Nakamura, Kosei; Kitaguchi, Tetsuya; Handa, Makoto; Watanabe, Kiyoaki; Fujimura, Yoshihiro; Yoshioka, Akira; Ikeda, Yasuo.

In: Biochemical and Biophysical Research Communications, Vol. 233, No. 3, 28.04.1997, p. 796-800.

Research output: Contribution to journalArticle

Iijima, Kaori ; Murata, Mitsuru ; Nakamura, Kosei ; Kitaguchi, Tetsuya ; Handa, Makoto ; Watanabe, Kiyoaki ; Fujimura, Yoshihiro ; Yoshioka, Akira ; Ikeda, Yasuo. / High shear stress attenuates agonist-induced, glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked. In: Biochemical and Biophysical Research Communications. 1997 ; Vol. 233, No. 3. pp. 796-800.
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AU - Nakamura, Kosei

AU - Kitaguchi, Tetsuya

AU - Handa, Makoto

AU - Watanabe, Kiyoaki

AU - Fujimura, Yoshihiro

AU - Yoshioka, Akira

AU - Ikeda, Yasuo

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