Modulation of macrophage tumoricidal capability by polyene antibiotics: support for membrane lipid as a regulatory determinant of macrophage function.

Abstract

The effects of the sterol-binding polyene antibiotics on macrophage tumoricidal capability was investigated. Incubation (for 2 h) of activated macrophages from BCG-infected mice with amphotericin B at 0.5-2 .mu.g/ml or amphotericin B methyl ester at 0.5-10 .mu.g/ml enhanced the capability of activated macrophages to kill [mouse fibroblast] 3T12 cells. These polyenes did not make normal or stimulated macrophages tumoricidal. Experiments with the ionophores gramicidin, alamethecin, nigericin and valinomycin indicate that the ionophoretic properties of amphotericin B may not account for its enhancing effect on macrophage tumoricidal potential. Two polyenes with a smaller ring structure, filipin and pimaricin, were also ineffective suggesting that stereospecific modifications in membrane lipid organization underlie the enhancing effect of amphotericin B. The clinical efficiency of amphotericin B in promoting resistance to fungal disease and possibly to neoplasia may operate in part through potentiation of macrophage effector functions.