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(Journal of Leukocyte Biology. 2001;69:248-252.)
© 2001 by Society for Leukocyte Biology

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

Andreas Kaufmann^*, Robert Salentin^*, Diethard Gemsa^* and Hans Sprenger

^* Institute of Immunology, Philipps University, Marburg; and
Institute of Laboratory Medicine, Leopoldina-Hospital, Schweinfurt, Germany

Correspondence: Andreas Kaufmann, Ph.D., Institute of Immunology, Philipps University Marburg, Robert-Koch-Str. 17, D-35037 Marburg, Germany. E-mail: kaufmana{at}mailer.uni-marburg.de

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 1 (MIP-1), which binds to CCR1 and CCR5. In striking contrast, differentiated macrophages displayed a strong chemotactic response to MIP-1 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.

Key Words: chemokine • chemokine receptors

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