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Macrophage colony-stimulating factor enhances the susceptibility of
macrophages to infection by human immunodeficiency virus and reduces the
activity of compounds that inhibit virus binding
A Bergamini, CF Perno, L Dini, M Capozzi, CD Pesce, L Ventura, L Cappannoli, L Falasca, G Milanese and R Calio
Department of Public Health, University of Rome Tor Vergata, Italy.
The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor
expression, susceptibility to human immunodeficiency virus type 1 (HIV)
infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were
studied in cultured, human primary macrophages. M-CSF stimulated macrophage
cells to express the CD4 receptor, and this resulted in an increase of both
the number of CD4+ cells and the density of the receptor on the cell
surface. M-CSF also significantly enhanced the susceptibility of macrophage
cells to HIV infection. Interestingly, the anti-HIV activity of dextran
sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding
with different mechanisms) was reduced 100-fold and fivefold, respectively,
in M-CSF- treated macrophages. Human blood concentrations of M-CSF are
reported to be similar to those used in this work (1,000 U/mL); thus, it is
conceivable that also in vivo this cytokine may modify the susceptibility
of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to
inhibit HIV replication. These results suggest that the in vitro study in
M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding
could provide further insights into the potential efficacy of these
compounds in patients.
Volume 84,
Issue 10,
pp. 3405-3412,
11/15/1994
Copyright © 1994 by The American Society of Hematology
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