© 2000 American Heart Association, Inc.
Thrombosis |
Platelet Thrombus Formation on Collagen at High Shear Rates Is Mediated by von Willebrand Factor–Glycoprotein Ib Interaction and Inhibited by von Willebrand Factor–Glycoprotein IIb/IIIa Interaction
Presented in part at a meeting of the American Society of Hematology, Orlando, Fla, December, 1996 (Blood. 1996;88:29a) and a meeting of the European Haematology Association, Paris, France, June, 1996 (Br J Haematol. 1996;93:180).
From the Department of Hematology, Graduate School of Biomembranes, University Medical Center, Utrecht, the Netherlands.
Correspondence to Dr J.J. Sixma, University Medical Center Utrecht, Department of Haematology (G03.647), PO Box 85.500/Heidelberglaan 100, 3508 GA Utrecht/3584 CX Utrecht, Netherlands. E-mail jsixma{at}lab.azu.nl
Abstract—We studied the role of
von Willebrand Factor (vWF) in platelet thrombus formation
in flowing blood by using a perfusion system and mutant forms of vWF
lacking either interaction with glycoprotein Ib (GpIb) or
with glycoprotein IIb/IIIa (
IIb-ß3). These
mutants were added to the blood of patients with severe von
Willebrand’s disease (vWD) or to normal blood reconstituted
with a human albumin solution instead of plasma. This blood was
then perfused over collagen type III spray-coated on a glass surface
and preincubated for 2 hours with 20 µg/mL plasma vWF. In this way,
the adhesion step was mediated by the preincubated plasma vWF bound to
collagen type III, whereas thrombus formation was mediated by mutant
vWF added to the perfusate. Thrombus formation was absent at
all 3 shear rates studied (300, 800, and 2600 s-1) when
A1-vWF, lacking interaction with GpIb, was added to the
perfusate, indicating the importance of GpIb-vWF interaction
for thrombus formation. The interaction of vWF and GpIb is currently
thought to be possible under physiological
conditions in which the conformation of vWF has been changed by
adsorption to a surface. Our results regarding the role of GpIb-vWF
interaction in thrombus formation suggest that a second mechanism may
operate by which a change may occur in GpIb on the surface of adhered
platelets either by activation of the molecule or as a consequence
of shear stress. Increased thrombus formation was observed when the
Arg-Gly-Gly-Ser–vWF, which does not interact with IIb-ß3,
was added to vWD blood and perfused at 2600 s-1. This
increase was not observed in vWD blood at lower shear rates or after
addition of Arg-Gly-Gly-Ser–vWF to reconstituted normal blood.
Thrombus formation at a high shear rate was largest when either vWF or
fibrinogen was present as a single ligand for IIb-ß3 at a high
shear rate. When both were present, thrombus formation was
decreased. We postulate that thrombus formation is less efficient
because of incomplete bridge formation when vWF and fibrinogen are both
present as ligands for IIb-ß3.
Key Words: von Willebrand factor • thrombus formation • GpIb • collagen
This article has been cited by other articles:
 |
|
 |
|
  F. Rodeghiero, G. Castaman, and A. Tosetto How I treat von Willebrand disease Blood, August 6, 2009; 114(6): 1158 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Chung, T. G. Popova, S. C. Jorgensen, L. Dong, V. Chandhoke, C. L. Bailey, and S. G. Popov Degradation of Circulating von Willebrand Factor and Its Regulator ADAMTS13 Implicates Secreted Bacillus anthracis Metalloproteases in Anthrax Consumptive Coagulopathy J. Biol. Chem., April 11, 2008; 283(15): 9531 - 9542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Bergmeier, C. L. Piffath, T. Goerge, S. M. Cifuni, Z. M. Ruggeri, J. Ware, and D. D. Wagner The role of platelet adhesion receptor GPIb{alpha} far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis PNAS, November 7, 2006; 103(45): 16900 - 16905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. J. Hulstein, P. G. de Groot, K. Silence, A. Veyradier, R. Fijnheer, and P. J. Lenting A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B Blood, November 1, 2005; 106(9): 3035 - 3042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, M. A. Cruz, and J. A. Lopez Identification of a Binding Site for Integrin {alpha}IIb{beta}3 in the von Willebrand factor (VWF) A1 Domain: Dual Roles for the A1 Domain in Platelet Thrombus Formation. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 3658 - 3658. [Abstract]
|
|
|
|
|
|
Y.-P. Wu, H. J. Bloemendal, E. E. Voest, T. Logtenberg, P. G. de Groot, M. F. B. G. Gebbink, and H. C. de Boer Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin Blood, August 15, 2004; 104(4): 1034 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. E. Kuijpers, V. Schulte, C. Oury, T. Lindhout, J. Broers, M. F. Hoylaerts, B. Nieswandt, and J. W. M. Heemskerk Facilitating roles of murine platelet glycoprotein Ib and {alpha}IIb{beta}3 in phosphatidylserine exposure during vWF-collagen-induced thrombus formation J. Physiol., July 15, 2004; 558(2): 403 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mekrache, C. Bachelot-Loza, N. Ajzenberg, A. Saci, P. Legendre, and D. Baruch Activation of pp125FAK by type 2B recombinant von Willebrand factor binding to platelet GPIb at a high shear rate occurs independently of {alpha}IIb{beta}3 engagement Blood, June 1, 2003; 101(11): 4363 - 4371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Remijn, Y.-P. Wu, E. H. Jeninga, M. J.W. IJsseldijk, G. van Willigen, P. G. de Groot, J. J. Sixma, A. T. Nurden, and P. Nurden Role of ADP Receptor P2Y12 in Platelet Adhesion and Thrombus Formation in Flowing Blood Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 686 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Candia, S. W. Hall, S. Rutella, R. Landolfi, R. K. Andrews, and R. De Cristofaro Binding of Thrombin to Glycoprotein Ib Accelerates the Hydrolysis of Par-1 on Intact Platelets J. Biol. Chem., February 9, 2001; 276(7): 4692 - 4698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Remijn, Y.-P. Wu, E. H. Jeninga, M. J.W. IJsseldijk, G. van Willigen, P. G. de Groot, J. J. Sixma, A. T. Nurden, and P. Nurden Role of ADP Receptor P2Y12 in Platelet Adhesion and Thrombus Formation in Flowing Blood Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 686 - 691. [Abstract] [Full Text] [PDF]
|
|