Journal of Biological Chemistry
Volume 272, Issue 5, 31 January 1997, Pages 2599-2606
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Cell Biology and Metabolism
Polyvalent Cationic Metals Induce the Rate of Transferrin-independent Iron Acquisition by HL-60 Cells*

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The trivalent metals iron, aluminum, and gallium greatly increase the rate of iron acquisition from low molecular weight chelates by human myeloid cells. The present study explores the mechanism responsible. Gallium-induced iron acquisition was shown to lead to stable cellular association of iron, the magnitude of which varied with the chelate to which the iron was bound. The majority of this iron initially associated with the plasma membrane. Cellular depletion of ATP did not affect the response to gallium nor did it require the continued presence of extracellular gallium. However, continued cell association of gallium was needed as subsequent cellular exposure to metal chelators resulted in a rapid loss of the “induced” phenotype. Other trivalent metals (lanthanum and gadolinium) and tetravalent metals (tin and zirconium) but not divalent metals also induced iron acquisition. Neither enhanced iron reduction nor protein kinase C or tyrosine kinases appeared involved in gallium-mediated induction of iron acquisition. Exposure of HL-60 cells to polyvalent cationic metals results in a dramatic and sustained increase in the rate of iron acquisition from low molecular weight chelating agents. This could be important for the rapid clearance of iron by phagocytes from the extracellular environment at sites of local tissue damage.

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*

This work was supported in part by research grants from the Office of Research and Development, Medical Research Service, Department of Veteran Affairs and National Institutes of Health Grants HL44275, AI28412, and DK25231. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Portions of this work have previously been presented in abstract form at meetings of the American Federation for Clinical Research and the Oxygen Society.