Some Factors Affecting the Release of Iron from Reticuloendothelial Cells

Abstract

S ummary . Factors modifying the release of iron from reticuloendothelial cells were studied in rats by injecting heat‐denatured erythrocytes containing [ 59 Fe]haemoglobin. The cells were rapidly taken up by the liver and spleen, and a proportion of the 59 Fe was released into the plasma, the maximum rate being between 1 and 4 hr after injection. The remaining 59 Fe was incorporated into storage compounds. A 10‐fold variation in the load of denatured erythrocytes produced a proportional change in the amount of iron released, the percentage remaining constant. Percentage release of 59 Fe was enhanced in venesected rats and diminished in hypertransfused rats. Release was inhibited by injecting either unlabelled denatured erythrocytes or iron bound with nitrilotriacetic acid (NTA‐iron) before the 59 Fe‐labelled cells, the maximum effect being obtained if the interval between the two injections was 3‐9 hr. Release was also inhibited by injecting NTA‐iron 30 min after the denatured labelled erythrocytes. Inhibition was always preceded by a rise in the serum‐iron concentration, and was associated with an increase in the percentage of 59 Fe incorporated into ferritin. It is postulated that the shortage of free transferrin binding sites for iron delays the entry of liberated haemoglobin iron into the plasma, and consequently there is enlargement of a ‘pre‐release’ iron pool. Other workers have shown that iron induces the synthesis of ferritin; the presence of a stimulated mechanism for ferritin synthesis within the reticuloendothelial cells would result in the diversion of an increased percentage of erythrocyte iron into storage compounds.