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*

*この研究の対応する著者

研究成果: Article査読

7 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)796-800
ページ数5
ジャーナルBiochemical and Biophysical Research Communications
233
3
DOI
出版ステータスPublished - 1997 4月 28

ASJC Scopus subject areas

  • 生化学
  • 生物理学
  • 分子生物学

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