Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood

• DOI: 10.1161/circulationaha.107.695189
• Publication Date: 2007-08-07T01:10:54Z
• Authors: Christian Schulz; Andreas Schäfer; Moritz Stolla; Sandra Kerstan; Michael Lorenz; Marie-Luise von B...; Matthias Schiemann; Johann Bauersachs; Torsten Gloe; Dirk H. Busch; Meinrad Gawaz; Steffen Massberg
• Keywords: CX3CR1; CX3CL1

The membrane-bound chemokine fractalkine (CX3CL1) is expressed on various cell types such as activated endothelial cells and has been implicated in the inflammatory process of atherosclerosis. aim present study was to dissect role leukocyte recruitment inflamed endothelium under arterial shear forces.With use immunofluorescence laminar flow assays, shows that human umbilical vein stimulated with tumor necrosis factor-alpha interferon-gamma abundantly express CX3CL1 promote substantial accumulation conditions. In presence high shear, firm adhesion leukocytes reduced by approximately 40% a function-blocking anti-fractalkine antibody or an directed against receptor (CX3CR1). With intravital video-fluorescence microscopy we demonstrate inhibition signaling attenuates atherosclerotic carotid artery apolipoprotein E-deficient mice, which suggests CX3CL1-CX3CR1 axis critically involved forces both vitro vivo. Surprisingly, platelets were strictly required for fractalkine-induced at rates. Correspondingly, specific platelet also significantly accumulation. We show soluble induces degranulation subsequent surface expression P-selectin, thereby promotes direct platelet-leukocyte interaction.Fractalkine triggers P-selectin exposure adherent platelets, initiates local essential step development lesions.