Published online before print September 11, 2003, doi: 10.1161/01.ATV.0000095360.62479.1F
© 2004 American Heart Association, Inc.
Brief Reviews |
Fractalkine in Vascular Biology
From Basic Research to Clinical Disease
From the Department of Rheumatology and Clinical Immunology (H.U.) and the Department of Hematology and Oncology (T.O), Clinical Science for Pathological Organs, Kyoto University Graduate School of Medicine, Kyoto, Japan; the Division of Cellular and Gene Therapies (HFM-518), Center for Biologics Evaluation and Research (E.T.B.), Food and Drug Administration, Bethesda, Md; the Department of Medicine, Osaka Dental University (Y.N.), Osaka, Japan; the Department of Microbiology, Kinki University School of Medicine (O.Y.), Osaka, Japan; and the Kan Research Institute (T.I.), Kyoto, Japan.
Correspondence to Hisanori Umehara, MD, PhD, Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail umehara{at}kuhp.kyoto-u.ac.jp
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-
and tumor necrosis factor-
. 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- 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.
Key Words: fractalkine • endothelial cells • vascular biology • atherosclerosis • inflammation
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