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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 875-883
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
Laura Fantuzzi,
Paola Borghi,
Veniero Ciolli,
George Pavlakis,
Filippo Belardelli, and
Sandra Gessani
From the Laboratory of Virology, Istituto Superiore di Sanità,
Rome; Drug Discovery Department, Istituto di Ricerca Cesare Serono,
Ardea, Italy; and the Human Retrovirus Section, National Cancer
Institute-Frederick Cancer Research and Development Center, ABL-Basic
Program, Frederick, MD.
Human peripheral blood monocytes differentiate into macrophages when
cultured in vitro for a few days. In the present study, we investigated
the expression of C-C chemokine and CXCR4 receptors in monocytes at
different stages of differentiation. Culturing of monocytes for 7 days
resulted in a progressive decrease of the mRNA that encodes for CCR2
and CCR3, whereas the expression of mRNA for other chemokine receptors
(CCR1, CCR4, CCR5, and CXCR4) was not substantially affected. The loss
of CCR2 mRNA expression in 7-day-cultured macrophages was associated
with a strong reduction in the receptor expression at the plasma
membrane, as well as in the monocyte chemotactic protein (MCP-1)
binding, as compared with freshly isolated monocytes. Furthermore, the
biologic response to MCP-1, as measured by intracellular calcium ions
increase and chemotactic response, was lost in 7-day-cultured
macrophages. Differentiation of monocytes into macrophages also
resulted in an increased secretion of MCP-1 that, at least in part, was
responsible for the downmodulation of its receptor (CCR2). The loss of
CCR2 expression and the parallel increase of MCP-1 secretion triggered by differentiation may represent a feedback mechanism in the regulation of the chemotactic response of monocytes/macrophages.
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