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Abstract
Platelet membrane glycoproteins Ib (GPIb) and ![Math Eq]()
(![Math Eq]()
) bind soluble von Willebrand factor (vWf) after stimulation with ristocetin (GPlb)
or with thrombin or ADP (![Math Eq]()
). In fluid-phase, vWf does not bind to these platelet receptors without stimulation.
In contrast, platelets adhere to solid-phase vWf without stimulation by ristocetin,
adenosine diphosphate (ADP), or thrombin, and adhesion increases after stimulation
by these agonists. The effect of monoclonal antibodies specific for GPIb (6D1) and
![Math Eq]()
(10E5 and HP1-1D) on platelet adhesion to solid-phase vWF was studied. Adhesion of
radiolabeled, washed platelets (with washed red blood cells) aspirated at a constant
wall shear rate of 1000 sec−1 through glass capillary tubes coated with purified human vWf was quantified. Unstimulated
platelet adhesion was decreased 80% to 90% by blocking either the GPIb site or the
![Math Eq]()
site with 6D1 or 10E5, respectively, or with 6D1 and 10E5 together. Adhesion was
not reduced significantly by HP1-1D (![Math Eq]()
). After stimulation with ADP or thrombin, the platelet adhesion was reduced by prior
incubation with saturating concentrations of either 6D1 (61% reduction) or 10E5 (80%
reduction), as well as with both 6D1 and 10E5 (80% reduction). After stimulation with
ristocetin, the adhesion was reduced with either 6D1 (90% reduction) or 10E5 (90%
reduction) or both 6D1 and 10E5 (90% reduction). Prior incubation with HP1-1D had
minimal effect on platelet adhesion to vWF after stimulation with thrombin, ADP, or
ristocetin. Monoclonal antibody HP1-1D (10 to 25 μg/ml) abolished iodine 125-labeled
fibrinogen binding to washed platelets (ADP- or thrombin-stimulated) but did not affect
125I-labeled vWf binding to washed, thrombin-stimulated platelets. These data demonstrate
that adhesion of stimulated or unstimulated platelets to solid-phase vWf is dependent
on both GPIb and ![Math Eq]()
. In addition, the data indicate that the binding of vWf and fibrinogen to the ![Math Eq]()
site may involve more than one binding site on the ![Math Eq]()
molecule.
(
) bind soluble von Willebrand factor (vWf) after stimulation with ristocetin (GPlb)
or with thrombin or ADP (
). In fluid-phase, vWf does not bind to these platelet receptors without stimulation.
In contrast, platelets adhere to solid-phase vWf without stimulation by ristocetin,
adenosine diphosphate (ADP), or thrombin, and adhesion increases after stimulation
by these agonists. The effect of monoclonal antibodies specific for GPIb (6D1) and
(10E5 and HP1-1D) on platelet adhesion to solid-phase vWF was studied. Adhesion of
radiolabeled, washed platelets (with washed red blood cells) aspirated at a constant
wall shear rate of 1000 sec−1 through glass capillary tubes coated with purified human vWf was quantified. Unstimulated
platelet adhesion was decreased 80% to 90% by blocking either the GPIb site or the
site with 6D1 or 10E5, respectively, or with 6D1 and 10E5 together. Adhesion was
not reduced significantly by HP1-1D (
). After stimulation with ADP or thrombin, the platelet adhesion was reduced by prior
incubation with saturating concentrations of either 6D1 (61% reduction) or 10E5 (80%
reduction), as well as with both 6D1 and 10E5 (80% reduction). After stimulation with
ristocetin, the adhesion was reduced with either 6D1 (90% reduction) or 10E5 (90%
reduction) or both 6D1 and 10E5 (90% reduction). Prior incubation with HP1-1D had
minimal effect on platelet adhesion to vWF after stimulation with thrombin, ADP, or
ristocetin. Monoclonal antibody HP1-1D (10 to 25 μg/ml) abolished iodine 125-labeled
fibrinogen binding to washed platelets (ADP- or thrombin-stimulated) but did not affect
125I-labeled vWf binding to washed, thrombin-stimulated platelets. These data demonstrate
that adhesion of stimulated or unstimulated platelets to solid-phase vWf is dependent
on both GPIb and 
. In addition, the data indicate that the binding of vWf and fibrinogen to the 
site may involve more than one binding site on the 
molecule.Abbreviations:
ADP (adenosine diphosphate), BSS (balanced salt solution), GPIb (platelet membrane glycoprotein Ib), GPIIbIIIa (platelet membrane glycoprotein IIbIIIa complex), HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), IgG (immunoglobulin G), SHPP (sulfosuccinimi-dyl-3-(4-hydroxyphenyl) propionate), vWf (von Willebrand factor)To read this article in full you will need to make a payment
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References
- The interaction between collagens and factor VIII von Willebrand factor: Investigation of the structural requirements for interaction.Thromb Res. 1983; 32: 545-556
- Correction by factor VII of the impaired platelet adhesion to subendothelium in von Willebrand's disease.Blood. 1978; 51: 267-279
- Decreased adhesion to platelets to subendothelium in von Willebrand's disease.J Lab Clin Med. 1974; 83: 296-300
- Adhesion of human blood platelets to human artery subendothelium is mediated by factor VIII-von Willebrand factor bound to subendothelium.Nature. 1979; 279: 636-638
- Platelets have more than one binding site for von Willebrand factor.J Clin Invest. 1983; 72: 1-12
- Glanzmann thromboasthenia: deficient binding of von Willebrand factor to thrombin stimulated platelets.in: Proc Natl Acad Sci USA. 79. 1982: 6038-6041
- Hemostatic plug formation in normal and von Willebrand pigs: The effect of the administration of cryoprecipitate and monoclonal antibody to von Willebrand factor.Blood. 1986; 67: 1229-1239
- Studies with a murine monoclonal antibody that abolishes ristocetin induced binding of von Willebrand factor to platelets: additional evidence in support of GPIb as a platelet receptor for von Willebrand factor.Blood. 1983; 61: 99-110
- Demonstration and characterization of specific binding sites for factor VIII/von Willebrand factor on human platelets.J Clin Invest. 1979; 63: 656-664
- Decreased adhesion of giant (Bernard-Soulier) platelets to subendothelium.Am J Med. 1974; 57: 920-925
- Specific roles for surface glycoproteins in platelet function.Nature. 1975; 255: 720-722
- Molecule defects in interaction of platelets with the vessel wall.N Engl J Med. 1984; 311: 1084-1098
- Binding of radioiodinated human von Willebrand factor to Bernard Soulier, thrombasthenic and von Willebrand platelets.Thromb Res. 1980; 19: 21-27
- Related binding mechanisms for fibrinogen, fibronectin, von Willebrand factor, and thrombospondin on thrombin-stimulated human platelets.Blood. 1985; 66: 724-727
- Interaction of asialo von Willebrand factor with glycoprotein Ib induces fibrinogen binding to the glycoproteinJ Clin Invest. 1985; 75: 1198-1203
![Math Eq]()
complex and mediates platelet aggregation. - Thrombin induced exposure and prostacyclin inhibition of the receptor for factorJ Clin Invest. 1982; 69: 1212-1222
![Math Eq]()
Willebrand factor on human platelets. - Adenosie diphosphate induces binding of von Willebrand factor to human platelets.Nature. 1982; 297: 154-156
- Morphological, biochemical and functional changes in human platelets subjected to shear stress.J Lab Clin Med. 1975; 86: 462-471
- Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation.J Clin Invest. 1986; 78: 1456-1461
- Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.Blood. 1988; 71: 1366-1374
- Adhesion of human platelets to purified solid-phase von Willebrans factor: studies of normal and Bernard-Soulier platelets.Thromb Res. 1983; 32: 115-122
- Adhesion of platelets to purified solid-phase von Willebrand factor: effects of wall shear rate, ADP, thrombin, and ristocetin.J Lab Clin Med. 1989; 114: 6-18
- Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIa complex at high shear rate.J Clin Invest. 1989; 83: 288-297
- The role of platelet membrane glycoproteins Ib and IIb-IIIa in platelet adherence to human artery subendothelium.Br J Haematol. 1985; : 681-691
- Platelet adhesion and thrombus formation on subendothelium by platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules.Blood. 1986; 67: 322-330
- Monoclonal antibodies to the glycoprotein IIb-IIIa epitopes involves in adhesive protein binding: effects on platelet spreading and ultrastructure on human arterial subendothelium.J Lab Clin Med. 1987; 109: 495-503
- von Willebrand factor-mediated platelet adhesion to collagen involves platelet membrane glycoprotein IIb-IIIa as well as glycoprotein Ib.J Lab Clin Med. 1988; 112: 58-67
- Modulation of platelet function through adhesion receptors: a dual role for glycoprotein IIbIIIa (integrin allbβ3) mediated by fibrinogen and glycoprotein Ib-von Willebrand Factor.J Biol Chem. 1992; 267: 11300-11306
- Identification of human megakaryocyte coagulation factor V.Blood. 1985; 65: 1396-1406
- CFU-M-derived human megakaryocytes synthesize glycoproteins IIb and IIIa.Blood. 1986; 67: 682-688
- Fibrin protofibril and fibrinogen binding to ADP stimulated platelets: evidence for a common mechanism.Biochim Biophys Acta. 1988; 968: 24-35
- Von Willebrand factor competes with fibrin for occupancy of GPIIbIIIa on thrombinstimulated platelets.Blood. 1990; 75: 889-894
- A rapid assay for von Willebrand factor.Thromb Res. 1988; 51: 461-468
- Purification of factor VIII complex.Thromb Res. 1984; 35: 431-450
- Selective enzyme purification by affinity chromatography.in: Proc Natl Acad Sci. 61. 1968: 636-643
- The labeling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent.Biochem J. 1973; 133: 529-539
- Chromatographie purification of fibrinogen.in: Laki K Fibrinogen. Marcel Dekker Inc, New York1968: 39
- Isolation of human platelets from plasma by centrifugation and washing.Methods Enzymol. 1989; 169: 3-11
- Structure and deformation properties of red blood cells: concepts and quantitative methods.Methods Enzymol. 1989; 173: 3-35
- Platelet adhesion and release: interfacial concentration of release materials.Am J Physiol. 1981; 240: H99-H108
- Separation of human platelets from plasma proteins including factor VIII-vWF by a combined albumin gradient-gel filtration method using HEPES buffer.Thromb Res. 1978; 12: 297-306
- Inhibition of von Willebrand factor-platelet interaction by fibrinogen.Nature. 1984; 308: 648-649
- A murine antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa.J Clin Invest. 1983; 72: 325-338
- Conconavalin A induces patching/capping of the platelet membrane glycoproteinThromb Haemost. 1988; 59: 281-283
![Math Eq]()
complex. - Platelet morphologic changes and fibrinogen receptor localization: initial responses in ADP-activated human platelets.Am J Pathol. 1992; 141: 707-719
- Independent modulations of von Wilebrand factor and fibrinogen binding to the platelet membrane glycoproteinJ Clin Invest. 1985; 76: 1950-1958
![Math Eq]()
complex as demonstrated by monoclonal antibody. - Fibrinogen competes with von Willebrand factor for binding to the glycoproteinBlood. 1984; 64: 797-800
![Math Eq]()
complex when platelets are stimulated with thrombin. - The effect of arg-gly-asp containing peptides on fibrinogen and von Willebrand factor binding to platelets.in: Proc Natl Acad Sci USA. 82. 1985: 8057-8061
- ADP-dependent common receptor mechanism for binding of von Willebrand factor and fibrinogen to human platelets.in: Proc Natl Acad Sci USA. 81. 1984: 4935-4939
complex and mediates platelet aggregation.
Willebrand factor on human platelets.
complex.
complex as demonstrated by monoclonal antibody.
complex when platelets are stimulated with thrombin.Article info
Publication history
Accepted:
February 16,
1994
Received in revised form:
February 15,
1994
Received:
August 20,
1993
Footnotes
☆Supported by Public Health Service Grants HL-28799 (J.D.O.) and HL-17430 (W.L.N.) from the National Heart, Lung, and Blood Institute.
☆☆Presented in part at the meeting of the Federation of American Associations for Experimental Biology, April, 1987.
Identification
Copyright
© 1994 Published by Elsevier Inc.
