Functions of fractalkine and its receptor CX3CR1 in monocyte recruitment during atherosclerosis. The recruitment of blood monocytes to the arterial intima is one of the earliest events in the formation of an atherosclerotic lesion and persists even in advanced lesions. Monocyte emigration is a multistep process that includes tethering and rolling, arrest, stable adhesion, and diapedesis (transendothelial migration). Shortly after initial tethers are established through binding of selectins or VCAM-1 on activated endothelium, monocytes encounter chemokines bound to endothelial cell–surface proteoglycans. Chemokines initiate signaling via chemokine G protein–coupled receptors, which then activates monocyte integrins and subsequently leads to reorganization of the cytoskeleton. Activated integrins mediate arrest and stable adhesion, and contribute to diapedesis by binding immunoglobulin gene superfamily adhesion molecules, including VCAM-1 and ICAM-1. Fractalkine, like other chemokines, activates multiple intracellular signaling pathways via its receptor. However, it is unique, since it is a transmembrane protein that binds to CX3CR1 rapidly and firmly, which may directly contribute to monocyte tethering and arrest. During atherogenesis, monocytes recruited to the arterial intima transform into macrophages, engulf lipids, and exhibit morphological features of foam cells.