title: Direct demonstration of radiolabeled von Willebrand factor binding to platelet glycoprotein Ib and IIb-IIIa in the presence of shear stress.
abstract: 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.
authors.affiliation: Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX 77251, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: McCrary
authors.forename: L H
authors.initials: LH
authors.lastname: Nolasco
authors.forename: J D
authors.initials: JD
authors.lastname: Hellums
authors.forename: M H
authors.initials: MH
authors.lastname: Kroll
authors.forename: N A
authors.initials: NA
authors.lastname: Turner
authors.forename: J L
authors.initials: JL
authors.lastname: Moake
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D010725:Phosphocreatine; D012310:Ristocetin; D003402:Creatine Kinase