T. Kurihara et al., DEFECTS IN MACROPHAGE RECRUITMENT AND HOST-DEFENSE IN MICE LACKING THE CCR2 CHEMOKINE RECEPTOR, The Journal of experimental medicine, 186(10), 1997, pp. 1757-1762
Chemokines are a structurally related family of cytokines that are imp
ortant for leukocyte trafficking. The C-C chemokine monocyte chemoattr
actant protein-1 (MCP-1) is a potent monocyte activator in vitro and h
as 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 homologu
es. CCR2 has also recently been demonstrated to be a fusion cofactor f
or several HIV isolates. To investigate the normal physiological funct
ion of CCR2, we generated mice with a targeted disruption of the ccr2
gene. Mice deficient for CCR2 developed normally and had no hematopoie
tic abnormalities. However, ccr2(-/-) mice failed to recruit macrophag
es in an experimental peritoneal inflammation model. In addition, thes
e mice were unable to clear infection by the intracellular bacteria, L
isteria monocytogenes. These results suggest that CCR2 has a nonredund
ant role as a major mediator of macrophage recruitment and host defens
e against bacterial pathogens and that MCP-1 and other CCR2 ligands ar
e effectors of those functions.