title: Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor.
abstract: We have identified two distinct mechanisms initiating the adhesion of flowing platelets to thrombogenic surfaces. The intergrin alpha IIb beta 3 promotes immediate arrest onto fibrinogen but is fully efficient only at wall shear rates below 600-900 s-1, perhaps because of a relatively slow rate of bond formation or low resistance to tensile stress. In contrast, glycoprotein Ib alpha binding to immobilized von Willebrand factor (vWF) appears to have fast association and dissociation rates as well as high resistance to tensile stress, supporting slow movement of platelets in continuous contact with the surface even at shear rates in excess of 6000 s-1. This eventually allows activated alpha IIb beta 3 to arrest platelets onto vWF under conditions not permissive of direct binding to fibrinogen. The coupling of these different functions may be crucial for thrombogenesis.
authors.affiliation: Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, La Jolla, California 92037, USA.
authors.forename: B
authors.initials: B
authors.lastname: Savage
authors.forename: E
authors.initials: E
authors.lastname: Saldívar
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ruggeri
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D018715:Microscopy, Video; D008969:Molecular Sequence Data; D015539:Platelet Activation; D010973:Platelet Adhesiveness / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D013718:Tensile Strength; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C032193:glycoprotein receptor GPIb-IX; D014841:von Willebrand Factor; D005337:Fibrin; D005340:Fibrinogen; D000527:Alprostadil