A study of iron transfer from rabbit transferrin to reticulocytes using synthetic chelating agents

Abstract

1. 1. The mechanism of uptake and utilization of transferrin-bound iron by reticulocytes was investigated using synthetic chelating agents either as inhibitors of iron uptake or as iron donors for the cells. It was found that 2,2′-bipyridine and 1,1-phenanthroline inhibited the uptake of transferrin-bound iron while EDTA, desferrioxamine, nitrilotriacetic acid, citrate and N- β-hydroxyethyliminodiacetic acid had little or no effect at the concentrations used. 2. 2. In the presence of intact reticulocytes or bone marrow cells, but not with mature erythrocytes or slices from several different tissues, iron was rapidly transferred from transferrin to bipyridine by a process which depended upon cellular metabolism and integrity. Radioiron bound to citrate, nitrilotriacetic acid, or N- β-hydroxyethliminodiacetic acid was also utilized for haemoglobin synthesis by reticulocytes, but was transferred to bipyridine by mature erythrocytes, haemolysed erythrocytes and other tissues as well as by reticulocytes. The results suggest that bipyridine and 1,10-phenanthroline inhibit reticulocyte utilization of iron by entering the cells and competing with a normal intracellular ferrous-iron acceptor. The assimilation of transferrin-bound iron differs from that of iron bound to citrate, nitrilotriacetic acid or N- β-hydroxyethyliminodiacetic acid in that transferrin must be taken up by the cells and its iron released by processes dependent on cell integrity and active metabolism, while the uptake and release of iron from the synthetic chelators is a passive process.