The amount of radioiron released from rat peritoneal macrophages after phagocytosis of 59Fe labelled erythrocytes can be enhanced by addition of desferrioxamine. The effect is dose dependent and the iron chelated by desferrioxamine appears to be at the expense of ferritin. However, desferrioxamine does not appear to chelate iron already incorporated into ferritin. It seems likely that the iron comes from a labile chelatable pool through which the iron from haemoglobin catabolism passes before being incorporated into ferritin. The desferrioxamine appears to enter the macrophage and chelate iron to form ferrioxamine which subsequently leaves the macrophage. In vivo it was not possible to show substantial iron chelaton by desferrioxamine in rats when 59Fe labelled non-viable red cells were injected intravenously. This suggests that in vivo mobilization of reticuloendothelial iron by desferrioxamine may be of limited significance.

Over the last 17 years there has been a significant reduction in the prevalence and severity of dietary iron overload in urban blacks of Johannesburg. This is attributed to a decrease in the consumption of traditionally brewed beer of high iron content over this period. A 40% reduction was found in hepatic iron concentrations measured in necropsy specimens from 248 male patients who died in 1976 as compared with 220 who died in 1959 and 1960. While hepatic iron concentrations rose with age in both groups there was no evidence of iron accumulation during the period between the two studies. Hepatic iron concentrations measured in 345 female subjects were many fold less than those of males and the 1976 group did not differ significantly from the 1959 to 1960 group. A paradoxical increase in the prevalence of portal fibrosis and cirrhosis was seen and may be due to the effects of increased ingestion of spirits and fortified wine in recent years. Iron overload was significantly greater in males with carcinoma of the esophagus and in those with idiopathic heart failure when compared to subjects who died of other causes. This suggests excessive exposure of these subjects to traditionally brewed beverages and the adulterants present in them.

The effect of endotoxin on the processing of erythrocyte iron by reticuloendothelial cells of the liver and spleen was studied in rats using heat damaged erythrocytes labelled with 59Fe. Endotoxin did not alter the uptake of the damaged cells but markedly inhibited the subsequent early phase of iron release from the reticuloendothelial cells. The inhibition seemed to be due to both a decreased rate of labelled haem destruction and an increased incorporation of radioiron into ferritin. Although early iron release was decreased 0--2 h after endotoxin administration, the diversion of iron into ferritin was more marked when endotoxin was given 18 h before. The block in iron release was partially overcome in animals that had been kept on an iron free diet or had been phlebotomised. In these animals the decreased rate of haem catabolism remained unaltered but less iron was diverted into ferritin.

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.

S ummary . Repeated injections of desferrioxamine significantly depleted the hepatic and splenic iron stores in normal rats, but not in rats which had been hyper‐transfused so as to reduce the rate of release of iron into the plasma. These observations indicate that the storage compounds ferritin and haemosiderin are not important direct donors of iron to desferrioxamine. Since plasma iron is not bound by the chelate, some compound or compounds on the pathway between the stores and the plasma is probably the major immediate source. By differentially labelling the iron in hepatic parenchymal cells and reticulo‐endothelial cells with 59 Fe, evidence was obtained that desferrioxamine chelates iron in both cell types.