Loss of CCR2 expression and functional response to monocyte chemotactic protein (MCP-1) during the differentiation of human monocytes: Role of secreted MCP-1 in the regulation of the chemotactic response
L. Fantuzzi et al., Loss of CCR2 expression and functional response to monocyte chemotactic protein (MCP-1) during the differentiation of human monocytes: Role of secreted MCP-1 in the regulation of the chemotactic response, BLOOD, 94(3), 1999, pp. 875-883
Human peripheral blood monocytes differentiate into macrophages when cultur
ed in vitro for a few days. In the present study, we investigated the expre
ssion of C-C chemokine and CXCR4 receptors in monocytes at different stages
of differentiation. Culturing of monocytes for 7 days resulted in a progre
ssive decrease of the mRNA that encodes for CCR2 and CCR3, whereas the expr
ession of mRNA for other chemokine receptors (CCR1, CCR4, CCR5, and CXCR4)
was not substantially affected. The loss of CCR2 mRNA expression in 7-day-c
ultured macrophages was associated with a strong reduction in the receptor
expression at the plasma membrane, as well as in the monocyte chemotactic p
rotein (MCP-1) binding, as compared with freshly isolated monocytes. Furthe
rmore, the biologic response to MCP-1, as measured by intracellular calcium
ions increase and chemotactic response, was lost in 7-day-cultured macroph
ages, Differentiation of monocytes into macrophages also resulted in an inc
reased secretion of MCP-1 that, at least in part, was responsible for the d
ownmodulation of its receptor (CCR2). The loss of CCR2 expression and the p
arallel increase of MCP-1 secretion triggered by differentiation may repres
ent a feedback mechanism in the regulation of the chemotactic response of m
onocytes/macrophages. (C) 1999 by The American Society of Hematology.