The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium

In a reconstituted flow chamber system, preincubation with chemokines can t rigger the arrest of rolling monocytes, suggesting that this interaction co uld help recruit these cells to early atherosclerotic lesions. To date, how ever, the contribution of endothelium-derived chemokines found in these les ion to monocyte arrests has not been investigated. The endothelium of lesio n-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE ( mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic ce ll line or mouse blood monocytes perfused through carotid arteries of ApoE( -/-) mice was reduced by treating with either pertussis toxin, an antagonis t of CXCR2, or an antibody to KC, but this process was insensitive to agent s that blocked CCR-2 or JE. Conversely, monocyte accumulation more than dou bled upon pre-perfusion of the carotid artery with KC but not with mouse MC P-1. Blockade Of alpha (4)beta (1) integrin (VLA-4) or vascular cell adhesi on molecule-1, but not CD18 or intercellular adhesion molecule-1, almost co mpletely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-d ependent monocyte recruitment.