We have shown that gallium (Ga) markedly increases transfem'n-lndependent acquisition of iron (Fe) by myelokl cells and cell lines (e.g. HL-60). Although others have demonstrated transfem'n-independent iron acquisition by non-myelokJ cells, the ability of Ga or other trivalent metals to induce this process has not been extensively studied. Therefore, we examined the ability of a variety of cell lines to acquire Fe from NTA before and after a brief exposure to Ga. Cells were washed, suspended in HBSS (1×106/ml) and then preincubated with or without 1 mM Ga (NO3)3 at 37°C for 30 min. [50Fe]NTA was then added and cell-associated 50Fe was determined over time. Ten different cell lines (HL-60. K56, PLB, rat hepatocyte clone 9, 3T, CaCo, A54, Hep G, Jiyoye, and HeLa) were examined. Fe acquisition could be detected over 2 hrs using cells which had not been preincubated with Ga. Magnitudes of Fe acquisition varied with the cell type. In the presence of 1 mM Ga, these cells exhibited markedly enhanced Fe acquisition similar In magnitude and kinetics to HL-60 cells. Cytokines such as TNF, IL-1 and IFN-y modulate transferrin-receptor mediated Fe metabolism in myeloid cells. We therefore investigated the effect of various cytokines on transferrin-independent Fe acquisition by HL-60 cells. HL-60 cells were incubated with TNF, IL-, IFN-T , G-CSF, or GM-CSF for 3 hrs following which their uptake of 50Fe from NTA was measured. A 2-fold or less increase in Fe acquisition was observed after any of the cytokine treatments. This slight increase in Fe uptake was not inhibited by cydoheximide. Furthermore, cytokine treatment does not synergize with Ga treatment. When cytoklnetreated cells were then exposed to Ga, the cells exhibited similar rate and kinetics of Fe acquisition as cells which were never cytokine treated. These data indicate that: 1) many cell types possess a Ga-inducible mechanism of transferrin-independent Fe uptake; and 2) exposure to various cytokines has only a slight effect on this mechanism. The role of this process In cellular Fe metabolism and the mechanism involved require additional investigation.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)