LPS down-regulates the expression of chemokine receptor CCR2 in mice and abolishes macrophage infiltration in acute inflammation

Interactions between chemokines and their specific receptors are important for leukocyte trafficking, The CC-chemokine monocyte chemoattractant protei n-1 (MCP-1) and its specific receptor CCR2 are essential in monocytic infil tration and have been associated with several inflammatory diseases. It has been reported that several endotoxin and proinflammatory cytokines inhibit CCR2 expression in vitro in human monocytes, We report here that Lipo poly saccharides (LPS) down-regulated CCR2 expression both in vitro and in vivo. Injection of LPS into mice dramatically reduced the expression of CCR2 on time surface of peripheral blood cells and completely blocked macrophage in filtration into the peritoneal cavity in response to thioglycollate elicita tion. In addition, treatment of mice with LPS reduced their efficiency to c lear Listeria monocytogenes infection. These results suggest that down-regu lation of CCR2 and blockage of monocyte infiltration may contribute to the inhibition of macrophage function in vivo by a low dose of LPS.