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Thromb Haemost 1993; 69(05): 496-502
DOI: 10.1055/s-0038-1651640
Original Article
Platelets
Schattauer GmbH Stuttgart

Transmembrane Calcium Influx Associated with von Willebrand Factor Binding to GP Ib in the Initiation of Shear-Induced Platelet Aggregation

Yasuo Ikeda
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Makoto Handa
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Tetsuji Kamata
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Koichi Kawano
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Yohko Kawai
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Kiyoaki Watanabe
1   The Departments of Hematology and Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan
,
Keiko Kawakami
2   The Department of Chemical Engineering, Waseda University, Tokyo, Japan
,
Kiyotaka Sakai
2   The Department of Chemical Engineering, Waseda University, Tokyo, Japan
,
Mayumi Fukuyama
3   The Basic Research Institute, Toray Industries Inc., Kanagawa, Japan
,
Ichiro Itagaki
3   The Basic Research Institute, Toray Industries Inc., Kanagawa, Japan
,
Akira Yoshioka
4   The Department of Pediatrics, Nara Medical School, Nara, Japan
,
Zaverio M Ruggeri
5   The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine and Committee on Vascular Biology, The Scripps Research Institute, La Jolla, California, USA
› Author Affiliations
Further Information

Publication History

Received 12 November 1992

Accepted after revision 28 December 1992

Publication Date:
25 July 2018 (online)

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Summary

We found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two-to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+]i increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+]i and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.

 

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