Amphotericin-B and monensin potentiation of murine erythropoiesis in vitro: a possible role for sodium ions.
To study the role of monovalent cation flux in erythropoiesis we cultured mouse bone marrow cells with amphotericin B (AmB), monensin, valinomycin, or Etruscomycin. At low doses the polyene antibiotic AmB has been shown to increase cell permeability to Na+ and K+ and we found that it potentiated erythropoietin (epo)-stimulated erythroid-colony (CFU-E) and burst (BFU-E) growth at concentrations ranging from 0.5-1.0 micrograms/ml. Monensin, a sodium-specific ionophore, potentiated epo-stimulated erythroid growth at concentrations of 1-30 nM. On the other hand, a potassium-specific ionophore, valinomycin, did not cause potentiation, but rather suppressed epo-dependent colony formation. Etruscomycin, another polyene, but one which in mammalian cells increases ion permeability only at toxic concentrations, was also suppressive. Potentiating concentrations of AmB and monensin increased the sensitivity of CFU-E and BFU-E to epo and at saturating epo levels increased the numbers of erythroid colonies and bursts by about 40%. Neither AmB nor monensin stimulated erythroid growth in the absence of epo. We found a 20-fold difference in the AmB concentrations comprising the maximally potentiating dose in C57BL/6 and AKR marrow cultures. This is consistent with observed differences between these two mouse strains with regard to other effects of AmB on them, including the immunoadjuvant properties of AmB. Our results showing potentiation due to sodium ion flux may be related to previous work showing potentiation of erythroid differentiation caused by calcium ion flux, since sodium ion movement may directly affect the intracellular calcium ion concentration.
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000494:pharmacology*; D008155:Lucensomycin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008985:Monensin / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology*; D014634:Valinomycin / Q000494:pharmacology
D005663:Furans; D004921:Erythropoietin; D014634:Valinomycin; D008155:Lucensomycin; D000666:Amphotericin B; D008985:Monensin; D012964:Sodium