Effect of ferrous and ferric chelators on transferrin-iron-macrophage interactions

A study was done to evaluate the effect of ferrous and ferric chelators on the interaction between transferrin-iron and cultured human blood monocytes. This interaction has been previously shown to involve a specific receptor and vesicle protonation. Transferrin-iron uptake was significantly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine, and the inhibition was shown not to be a consequence of the mobilisation of intracellular iron by the chelator. Chase experiments and prolonged incubation studies suggested that the chelator prevented the iron released from transferrin from negotiating the unit membrane. The iron and transferrin then appeared to be returned independently to the incubation medium. In contrast, a hydrophilic ferrin chelator, desferrioxamine, had only a very modest effect on the interaction. These findings are compatible with the hypothesis that transferrin-iron is reduced to the ferrous state during its uptake by the culture human blood monocyte.