Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice

The chemokine receptors CCR2 and CCR5 play important roles in the recruitme nt of monocytes/macrophages and T cells. To better understand the role of b oth receptors in murine models of inflammatory diseases and to recognize po tential problems when correlating these data to humans, we have generated m Abs against murine CCR2 and CCR5. In mice CCR2 is homogeneously expressed o n monocytes and on 2-15% of T cells, closely resembling the expression patt ern in humans. In contrast to humans, murine NK cells are highly CCR5 posit ive. In addition, CCR5 is expressed on 3-10% of CD4 and 10-40% of CD8-posit ive T cells and is weakly detectable on monocytes. Using a model of immune complex nephritis, we examined the effects of inflammation on chemokine rec eptor expression and found a 10-fold enrichment of CCR5(+) and CCR2(+) T ce lls in the inflamed kidneys. The activity of various chemokines and the ant agonistic properties of the mAbs were measured by ligand-induced internaliz ation of CCR2 and CCR5 on primary leukocytes. The Ab MC-21 (anti-CCR2) redu ced the activity of murine monocyte chemotactic protein 1 by 95%, whereas t he Ab MC-68 (anti-CCR5) blocked over 99% of the macrophage-inflammatory pro tein 1 alpha and RANTES activity. MC-21 and MC-68 efficiently blocked the l igand binding to CCR2 and CCR5 with an IC50 of 0.09 and 0.6-1.0 mug/ml, res pectively. In good correlation to these in vitro data, MC-21 almost complet ely prevented the influx of monocytes in thioglycollate-induced peritonitis . Therefore, both Abs appear as useful reagents to further study the role o f CCR2 and CCR5 in murine disease models.