Direct demonstration of radiolabeled von Willebrand factor binding to platelet glycoprotein Ib and IIb-IIIa in the presence of shear stress.
In this study it is demonstrated for the first time that shear stress induces the binding of exogenous von Willebrand factor (vWF) multimers to platelets. The vWF preparations used were: 125I-vWF purified from human cryoprecipitate (and including all vWF multimers present in normal plasma); and 35S-cysteine-vWF secreted by human umbilical vein endothelial cells (HUVECs) (and containing unusually large vWF forms, as well as all plasma-type vWF multimers). Direct shear-induced binding to washed platelets (300-360 x 10(3)/microliters) of radiolabeled vWF was maximum at 60-120 dynes/cm2 evaluated at 30 sec and was in extent about one-quarter of the binding stimulated by ristocetin after 3 min of incubation. The shear-induced binding of only a small percentage of added radiolabeled vWF was sufficient to initiate aggregation. Radiolabeled vWF attached to both glycoprotein (GP) Ib and GPIIb-IIIa receptors in the shear field, with complete inhibition of binding occurring with simultaneous blockade of both receptors. Binding was potentiated by ADP released from sheared platelets.
McCrary
J K
JK
Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX 77251, USA.
Nolasco
L H
LH
Hellums
J D
JD
Kroll
M H
MH
Turner
N A
NA
Moake
J L
JL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D001809:Blood Viscosity; D003402:Creatine Kinase / Q000494:pharmacology; D018056:Hemorheology; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D010725:Phosphocreatine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011869:Radioligand Assay; D012016:Reference Values; D012310:Ristocetin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D010725:Phosphocreatine; D012310:Ristocetin; D003402:Creatine Kinase