title: The CX3C chemokine fractalkine mediates platelet adhesion via the von Willebrand receptor glycoprotein Ib.
abstract: The membrane-anchored CX3C chemokine fractalkine (FKN) is expressed on activated endothelium and is associated with the development of atherosclerosis. The potential of FKN in mediating platelet adhesion beyond platelet activation remains unexplored to date. A flow-based adhesion assay was used to study the adhesion of platelets to immobilized FKN under physiologic flow conditions. Platelet adhesion to von Willebrand factor (VWF) was increased in the presence of FKN at 600 inverse seconds. Additional platelet adhesion to FKN coimmobilized with VWF was dependent on the FKN receptor CX3CR1 and activation of glycoprotein (GP) IIb/IIIa. The number of platelets rolling on VWF was likewise enhanced in the presence of FKN. The enhancement of rolling on FKN and VWF was insensitive to anti-CX3CR1 antibody but was fully inhibited by neutralizing GPIbα function. The extracellular domain of GPIbα was covalently coupled to fluorescent microspheres, and microsphere binding was significantly higher in the presence of FKN. Platelet adhesion to activated endothelium in vitro and to intact human arteries was substantially increased in an FKN-dependent manner. These data demonstrate that endothelial expressed FKN activates platelets via its cognate receptor CX3CR1, whereas platelet adhesion is predominantly mediated by GPIbα and independent of CX3CR1.
authors.affiliation: Department of Clinical Pharmacology, J. W. Goethe University HospitalFrankfurt, Frankfurt, Germany. santos@med.uni-frankfurt.de
authors.forename: Sascha
authors.initials: S
authors.lastname: Meyer dos Santos
authors.forename: Ute
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: Klaus
authors.initials: K
authors.lastname: Scholich
authors.forename: Karen
authors.initials: K
authors.lastname: Nelson
authors.forename: Nadejda
authors.initials: N
authors.lastname: Monsefi
authors.forename: Hans
authors.initials: H
authors.lastname: Deckmyn
authors.forename: Karina
authors.initials: K
authors.lastname: Kuczka
authors.forename: Anita
authors.initials: A
authors.lastname: Zorn
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
mesh_terms: D001158:Arteries / Q000502:physiology; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D018056:Hemorheology; D006801:Humans; D066298:In Vitro Techniques; D010973:Platelet Adhesiveness / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors / Q000502:physiology; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000502:physiology; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor