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

Citation
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
Citations number
53
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
94
Issue
3
Year of publication
1999
Pages
875 - 883
Database
ISI
SICI code
0006-4971(19990801)94:3<875:LOCEAF>2.0.ZU;2-D
Abstract
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.