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

AUTOR(ES)

Chapman, H A

RESUMO

We have examined the effects of the sterol-binding polyene antibiotics on macrophage tumoricidal capability. Incubation for 2 hr of activated macrophages from bacillus Calmette-Guérin-infected mice with amphotericin B at 0.5--2 microgram/ml or amphotericin B methyl ester at 0.5--10 microgram/ml enhanced the capability of activated macrophages to kill 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 results suggest that the clinical efficacy of amphotericin B in promoting resistance to fungal disease and possibly to neoplasia may operate in part through potentiation of macrophage effector functions.

Documentos Relacionados

• Selective Membrane Toxicity of the Polyene Antibiotics: Studies on Natural Membranes
• Selective Membrane Toxicity of the Polyene Antibiotics: Studies on Lecithin Membrane Models (Liposomes)
• Repair of membrane alterations induced in baby hamster kidney cells by polyene macrolide antibiotics.
• Cholesterol requirement of mycoplasmas as determined by microtiter test using polyene antibiotics.
• Aminoglycoside antibiotics moderately impair granulocyte function.