title: Fractalkine in vascular biology: from basic research to clinical disease.
abstract: Fractalkine (now also called CX3CL1) is a unique chemokine that functions not only as a chemoattractant but also as an adhesion molecule and is expressed on endothelial cells activated by proinflammatory cytokines, such as interferon-gamma and tumor necrosis factor-alpha. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes, which contain high levels of intracellular perforin and granzyme B, and on macrophages. Soluble fractalkine causes migration of NK cells, cytotoxic T lymphocytes, and macrophages, whereas the membrane-bound form captures and enhances the subsequent migration of these cells in response to secondary stimulation with other chemokines. Furthermore, stimulation through membrane-bound fractalkine activates NK cells, leading to increased cytotoxicity and interferon-gamma production. Recently, accumulating evidence has shown that fractalkine is involved in the pathogenesis of various clinical disease states or processes, such as atherosclerosis, glomerulonephritis, cardiac allograft rejection, and rheumatoid arthritis. In addition, polymorphisms in CX3CR1, which reduce its binding activity to fractalkine, have been reported to increase the risk of HIV disease and to reduce the risk of coronary artery disease. This review will examine new concepts underlying fractalkine-mediated leukocyte migration and tissue damage, focusing primarily on the pathophysiological roles of fractalkine in various clinical conditions, especially in atherosclerosis and vascular injury.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Clinical Science for Pathological Organs, Kyoto University Graduate School of Medicine, Kyoto, Japan. umehara@kuhp.kyoto-u.ac.jp
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
authors.forename: Eda T
authors.initials: ET
authors.lastname: Bloom
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagano
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002318:Cardiovascular Diseases / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000737:chemistry / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D018121:Receptors, Cytokine / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV