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 protein-1 (MCP-1) and its specific receptor CCR2 are essential in monocytic infiltration 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 lipopolysaccharides (LPS) down-regulated CCR2 expression both in vitro and in vivo. Injection of LPS into mice dramatically reduced the expression of CCR2 on the surface of peripheral blood cells and completely blocked macrophage infiltration into the peritoneal cavity in response to thioglycollate elicitation. In addition, treatment of mice with LPS reduced their efficiency to clear Listeria monocytogenes infection. These results suggest that down-regulation of CCR2 and blockage of monocyte infiltration may contribute to the inhibition of macrophage function in vivo by a low dose of LPS.