Defects in Macrophage Recruitment and Host Defense in Mice Lacking the CCR2 Chemokine Receptor

作者：Takao Kurihara, Glenn A. Warr, James K. Loy, Rodrigo Bravo · 发表于：The Journal of Experimental Medicine · 年份：1997 · DOI：10.1084/jem.186.10.1757 · 被引用次数：722 · 研究领域：HIV Research and Treatment、Chemokine receptors and signaling、Immune Cell Function and Interaction

Chemokines are a structurally related family of cytokines that are important for leukocyte trafficking. The C-C chemokine monocyte chemoattractant protein-1 (MCP-1) is a potent monocyte activator in vitro and has been associated with monocytic infiltration in several inflammatory diseases. One C-C chemokine receptor, CCR2, has been identified that mediates in vitro responses to MCP-1 and its close structural homologues. CCR2 has also recently been demonstrated to be a fusion cofactor for several HIV isolates. To investigate the normal physiological function of CCR2, we generated mice with a targeted disruption of the ccr2 gene. Mice deficient for CCR2 developed normally and had no hematopoietic abnormalities. However, ccr2(-/-) mice failed to recruit macrophages in an experimental peritoneal inflammation model. In addition, these mice were unable to clear infection by the intracellular bacteria, Listeria monocytogenes. These results suggest that CCR2 has a nonredundant role as a major mediator of macrophage recruitment and host defense against bacterial pathogens and that MCP-1 and other CCR2 ligands are effectors of those functions.