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Enhancement of macrophage superoxide anion production by amphotericin B

Amphotericin B (AmB) appears to have some important immunomodulatory effects, but its mechanism of action has not been explained. We investigated the effects of AmB on activation of human monocyte-derived macrophages. Macrophages cultured in the presence of AmB had an enhanced capacity to produce superoxide anion after stimulation with phorbol myristate acetate. This enhancement was dose dependent within a therapeutic range of AmB levels (0.1 to 3.0 mg/liter). Macrophages cultured in the presence of AmB had enhanced surface expression of Ia antigen; phagocytosis of unopsonized zymosan, opsonized Staphylococcus aureus, or erythrocytes opsonized with C3bi or immunoglobulin G paradoxically appeared to be reduced, but results did not achieve statistical significance. AmB appears to activate macrophages and may do so via direct effects on the plasma membrane.