POLYVALENT CATIONIC METALS INDUCE THE RATE OF TRANSFERRIN-INDEPENDENTIRON ACQUISITION BY HL-60 CELLS

The trivalent metals iron, aluminum, and gallium greatly increase the rate of iron acquisition from low molecular weight chelates by human m yeloid cells. The present study explores the mechanism responsible. Ga llium-induced iron acquisition was shown to lead to stable cellular as sociation of iron, the magnitude of which varied with the chelate to w hich the iron was bound. The majority of this iron initially associate d with the plasma membrane. Cellular depletion of ATP did not affect t he response to gallium nor did it require the continued presence of ex tracellular gallium. However, continued cell association of gallium wa s needed as subsequent cellular exposure to metal chelators resulted i n a rapid loss of the ''induced'' phenotype. Other trivalent metals (l anthanum and gadolinium) and tetravalent metals (tin and zirconium) bu t not divalent metals also induced iron acquisition. Neither enhanced iron reduction nor protein kinase C or tyrosine kinases appeared invol ved in gallium-mediated induction of iron acquisition. Exposure of HL- 60 cells to polyvalent cationic metals results in a dramatic and susta ined increase in the rate of iron acquisition from low molecular weigh t chelating agents. This could be important for the rapid clearance of iron by phagocytes from the extracellular environment at sites of loc al tissue damage.