Increase of CCR1 and CCR5 expression and enhanced functional response to MIP-1 alpha during differentiation of human monocytes to macrophages

Chemokines and their receptors regulate migration of leukocytes under normal and inflammatory conditions. In this study, we analyzed the CC chemokine receptor (CCR) expression of monocytes differentiating in vitro to macrophages. We observed a time-dependent change of expression and functional responsiveness of CCR1, CCR2, and CCR5 within 48 h. Whereas freshly harvested monocytes were strongly attracted by monocyte chemotactic protein 1 (MCP-1), a specific ligand for CCR2, only a weak response was observed to macrophage inflammatory protein 1alpha (MIP-1alpha), which binds to CCR1 and CCR5. In striking contrast, differentiated macrophages displayed a strong chemotactic response to MIP-1alpha and only a weak response to MCP-1. These findings were paralleled by intracellular calcium shifts. During the time course of monocyte to macrophage differentiation, mRNA levels and surface expression of CCR2 decreased, whereas that of CCR1 and CCR5 increased. The time-dependent switch from CCR2 on monocytes to CCR1 and CCR5 on mature macrophages reflects a functional change belonging to the differentiation process of monocytes to macrophages and may form the basis for a differential responsiveness of monocytes and macrophages to distinct sets of chemokines.