Monoclonal antibodies to platelet glycoproteins Ib and IIb/IIIa inhibit adhesion of platelets to purified solid-phase von Willebrand factor.
Platelet membrane glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa) bind soluble von Willebrand factor (vWf) after stimulation with ristocetin (GPIb) or with thrombin or ADP (GPIIb/IIIa). 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 GPIIb/IIIa (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 GPIIb/IIIa site with 6D1 or 10E5, respectively, or with 6D1 and 10E5 together. Adhesion was not reduced significantly by HP1-1D (anti-GPIIb/IIIa). 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Danton
M C
MC
Department of Pathology, University of Iowa, Iowa City.
Zaleski
A
A
Nichols
W L
WL
Olson
J D
JD
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects* / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D012310:Ristocetin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism* / Q000502:physiology
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D012310:Ristocetin; D000244:Adenosine Diphosphate; D013917:Thrombin