Effect of lead on the transport of transferrin-free and transferrin-bound iron into rabbit reticulocytes

Abstract

The effects of Pb on iron transport into rabbit reticulocytes was investigated using two sources of iron, non-transferrin-bound ferrous iron, Fe(II), and transferrin-bound iron, and fractionating the cells into haem, cytosolic and stromal fractions. Uptake of Fe(II) into all three fractions was inhibited by low concentrations of Pb, 50% inhibition of uptake to the cytosol ( ic 50) occurring at 1 μM Pb. Fe(II) uptake could be divided into saturable and non-saturable components. The saturable component was inhibited at lower concentrations of Pb than the non-saturable component. Pb reduced the V max and increased the K m values for saturable Fe(II) transport. The effects of Pb on Fe(II) transport were reversible and were observed with PbCl 2 and Pb (NO 3) 2 as well as with lead acetate. Pb also inhibited the uptake of transferrin-bound iron but at higher concentrations ( ic 50, 4 μM) and the inhibition was less readily reversible. The effect was attributable to inhibition of transferrin endocytosis which resulted in a redistribution of transferrin receptors from intracellular to cell surface sites. These results show that Pb can inhibit transferrin endocytosis and iron transport across the cell membrane of reticulocytes and raise the possibility that these effects may contribute to the hypochromic anaemia associated with Pb poisoning, in addition to the previously established inhibition of enzymes of the haem synthesis pathway.