title: Fractalkine--a local inflammatory marker aggravating platelet activation at the vulnerable plaque.
abstract: Chemokines play an important role in inducing chemotaxis of cells, piloting white blood cells in immune surveillance and are crucial parts in the development and progression of atherosclerosis. Platelets are mandatory players in the initiation of atherosclerotic lesion formation and are susceptible targets for and producers of chemokines. Several chemokine receptors on platelets have been described previously, amongst them CX(3)CR1, the receptor for fractalkine. The unique chemokine fractalkine (CX(3)CR1, FKN) exists as a soluble as well as a membrane-anchored glycoprotein. Its essential role in the formation of atherosclerotic lesions and atherosclerosis progression has been impressively described in mouse models. Moreover, fractalkine induces platelet activation and adhesion via a functional fractalkine receptor (CX(3)CR1) expressed on the platelet surface. Platelet activation via the FKN/CX(3)CR1-axis triggers leukocyte adhesion to activated endothelium, and fractalkine-induced platelet P-selectin is mandatory for leukocyte recruitment under arterial flow conditions. This review summarises the role of fractalkine as a potential local inflammatory mediator which influences platelet activation in the setting of atherosclerosis. Beyond that, aspects of a potential interaction between fractalkine and platelet responsiveness to antiplatelet drugs are described. Furthermore, the possible impact of high-density lipoprotein cholesterol (HDL-C) on atherosclerosis progression, platelet activation and fractalkine signalling are discussed.
authors: Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors: Ulrike
authors: U
authors: Flierl
authors: Andreas
authors: A
authors: Schäfer
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D054428:Chemokine CX3CL1 / Q000502:physiology*; D018925:Chemokines / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D019007:P-Selectin / Q000502:physiology; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000378:metabolism* / Q000503:physiopathology; D015539:Platelet Activation; D019707:Receptors, Chemokine / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D012422:Rupture, Spontaneous; D015398:Signal Transduction / Q000502:physiology; D014657:Vasculitis / Q000097:blood / Q000503:physiopathology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D018925:Chemokines; D008076:Cholesterol, HDL; C515539:Cx3cl1 protein, mouse; D018836:Inflammation Mediators; D019007:P-Selectin; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV