EFFECTS OF AMPHOTERICIN B ON THE FUNCTION AND GENE EXPRESSION IN MACROPHAGE CELL LINES

Abstract

1) Amphotericin B (AMB) was found to suppress the chemotactic function of macrophage-like cell lines, CANS and HINS, in a dose-dependent manner. Marked suppression was observed 1 h after the AMB treatment. Nystatin and filipin also showed similar but weaker effect. 2) Spontaneous cytotoxicity to EL4 target by macrophage cell lines 2-6 h after the treatment with AMB differed among the cell lines; AMB enhanced the activity in CANS-31a, had no effect in CANS-83, and suppressed the activity in CANS-196 and HINS-B3 cells. However, the cytotoxic activity of all the macrophage cell lines was suppressed 12 h after the treatment. Less marked but similar effects were observed with nystatin and filipin. 3) Incubation with mouse interferon γ (IFN_γ) followed by lipopolysaccharide (LPS) markedly enhanced the expression of both H-2^ｄ and I-A^d antigens in CANS-31a and CANS-196 cell lines. AMB also induced a significant enhancement of H-2^d and I-A^d antigen expression. 4) Incubation with IFN_γ followed by LPS enhanced transcription of H-2 and β2-microglobulin (β2-m) genes in CANS-31a cells as the time of IFN_γ-treatment was lengthened. AMB also showed a less marked but similar effect in the same cell line. 5) AMB induced enhanced and prolonged transcription of c-fos and macrophage-specific MS2 and MS7 genes in CANS-31a cells. 6) The results suggest that AMB enhances the expression of various genes after forming complexes with sterols in the cell membrane ofmacrophage cell lines while inhibiting receptor-ligand interaction, leading to enhancement or suppression of the macrophage function.