Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.
We have used confocal videomicroscopy in real time to delineate the adhesive interactions supporting platelet thrombus formation on biologically relevant surfaces. Type I collagen fibrils exposed to flowing blood adsorb von Willebrand factor (vWF), to which platelets become initially tethered with continuous surface translocation mediated by the membrane glycoprotein Ib alpha. This step is essential at high wall shear rates to allow subsequent irreversible adhesion and thrombus growth mediated by the integrins alpha2beta1 and alpha(IIb)beta3. On subendothelial matrix, endogenous vWF and adsorbed plasma vWF synergistically initiate platelet recruitment, and alpha2beta1 remains key along with alpha(IIb)beta3 for normal thrombus development at all but low shear rates. Thus, hemodynamic forces and substrate characteristics define the platelet adhesion pathways leading to thrombogenesis.
Savage
B
B
The Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Almus-Jacobs
F
F
Ruggeri
Z M
ZM
D000818:Animals; D001783:Blood Flow Velocity; D001792:Blood Platelets / Q000502:physiology*; D002417:Cattle; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000097:blood / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology; D038981:Receptors, Collagen; D013927:Thrombosis / Q000097:blood*; D014471:Umbilical Veins
D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D038981:Receptors, Collagen