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

The effects of macrophage colony-stimulating factor (M-CSF) on CD4 rec eptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and solubl e-CD4 were studied in cultured, human primary macrophages. M-CSF stimu lated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4(+) cells and the density of t he receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, t he anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was re duced 100-fold and fivefold, respectively, in M-CSF-treated macrophage s. Human blood concentrations of M-CSF are reported to be similar to t hose used in this work (1,000 U/ mL); thus, it is conceivable that als o in vivo this cytokine may modify the susceptibility of macrophages t o HIV and the ability of dextran sulfate and soluble CD4 to inhibit HI V replication. These results suggest that the in vitro study in M-CSF- treated macrophages of promising drugs inhibitors of HIV-CD4 binding c ould provide further insights into the potential efficacy of these com pounds in patients. (C) 1994 by The American Society of Hematology.