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(Circulation Research. 2001;89:376.)
© 2001 American Heart Association, Inc.

Editorial

Cytokine Receptor CX3CR-1 and Fractalkine

New Factors in the Atherosclerosis Drama?

R. Wayne Alexander

From the Department of Medicine, Emory University School of Medicine, Atlanta, Ga.

Correspondence to R. Wayne Alexander, MD, PhD, Department of Medicine, Emory University Hospital, 1364 Clifton Rd Northeast, Atlanta, GA 30322. E-mail ralexan@emory.edu

Key Words: chemokine • receptor • polymorphisms • coronary disease

Atherosclerosis is a chronic inflammatory disease of the blood vessel wall that is characterized by the accumulation of mononuclear cells, which are transformed into tissue macrophages/foam cells, and of T cells. The general acceptance of this concept began in the late 1980s¹ and was soon followed by attempts to understand the mechanisms by which the leukocytes were attracted into the arterial wall. A general understanding previously had been achieved, in other inflammatory contexts, of the mechanisms of leukocyte-endothelial interactions in the form of rolling, adhesion, and migration from the blood compartment through the endothelium as a result of the actions of selectins, adhesion molecules, and chemotactic cytokines called chemokines.² Chemokines act through a specific family of receptors on leukocytes and other cells to activate high-affinity binding sites for counter receptors/adhesion molecules on endothelium. They also have potent chemoattractant activity-guiding leukocyte migration through tissues.

Chemokines constitute a large number of structurally related proteins that have been classified into families based on relative positions of cysteine (C) residues.² A prototype chemokine is monocyte chemoattractant protein-1 (MCP-1), which has been associated with the pathogenesis of atherosclerosis as discussed below. MCP-1, for example, belongs to the C-C family with adjacent cysteine residues. Fractalkine is a novel, recently discovered chemokine that belongs to the CXXXC (CX3C) family (X represents any amino acid).³ It exists in a membrane-bound form at the tip of a mucin-like stalk as well as in a soluble form. Fractalkine is particularly interesting for its potential as being pathophysiologically important in atherosclerosis. . . . [Full Text of this Article]

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