MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions

Monocytes contribute to the development of atherosclerotic lesions in mouse models(1-3), The chemoattractant proteins (chemokines), monocyte chemoattr actant protein-1 (MCP-1) and interleukin-8 (IL-8), are found in human ather oma(4,5), and mice lacking receptors for these chemokines are less suscepti ble to atherosclerosis and have fewer monocytes in vascular lesions(6,7). A lthough MCP-1 has a powerful effect on monocytes, IL-8 is thought to act pr edominantly on neutrophils and it is unclear how it could recruit monocytes (6,8). Here we investigate the ability of chemokines to control the interac tion of monocytes under now conditions with vascular endothelium that has b een transduced to express specific leukocyte-adherence receptors. We find t hat MCP-I and IL-8 can each rapidly cause rolling monocytes to adhere firml y onto monolayers expressing E-selectin, whereas related chemokines do not. These effects do not correlate with either the induction of a calcium tran sient or chemotaxis. We conclude that chemokines are important modulators o f monocyte-endothelial interactions under now conditions. Moreover, our fin ding that IL-8 is a powerful trigger for firm adhesion of monocytes to vasc ular endothelium reveals an unexpected role for this chemokine in monocyte recruitment.