title: GPIb potentiates GPVI-induced responses in human platelets.
abstract: Platelet adhesion to vascular subendothelial proteins at the site of blood vessel injury is critical for initiating haemostasis. Collagen is a major matrix protein that binds plasma von Willebrand factor (vWF) when the endothelium becomes damaged and therefore in vivo platelets are likely to encounter both of these agonists simultaneously, through glycoprotein VI (GPVI) and alpha2beta1 receptors for collagen and GPIb-V-IX and alphaIIbbeta3 receptors for vWF. We hypothesised a potentiatory role for vWF that would synergise with collagen leading to functional activation and show this to be the case for platelet aggregation, 5-HT secretion and calcium responses. Synergy between these two agonists is likely to involve receptors GPVI and GPIb-V-IX, for collagen and vWF, respectively, since 5-HT secretion in response to collagen is potentiated by vWF in the presence of either EGTA or EDTA, which prevent binding to integrins alphaIIbbeta3 (EGTA) or both alphaIIbbeta3 and alpha2beta1 (EDTA). In addition, vWF is also able to potentiate 5-HT secretion responses to collagen-related peptide, confirming that GPVI is able to support synergy with vWF. These findings are important in that they reveal a novel role for vWF in platelet activation as a potentiator of platelet activation by collagen.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Baker
authors.forename: Rebecca K L
authors.initials: RK
authors.lastname: Griggs
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Falati
authors.forename: Alastair W
authors.initials: AW
authors.lastname: Poole
mesh_terms: D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007700:Kinetics; D015539:Platelet Activation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D020239:Receptor Cross-Talk; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D012701:Serotonin