Ferritin synthesis by monocyte-derived macrophages in thalassemic patients with intrinsic iron overload.

Macrophage ferritin content was determined following culture of peripheral blood monocytes for a period of 8 d in 40% autologous plasma to render them mature macrophages. Ferritin content was measured prior to and following culture using the radioimmunoassay. The normal range of values was established in a group of 22 healthy volunteer blood donors. A significant increase in the ratio of macrophage/monocyte ferritin was observed in every donor studied (range 1.2 - 1.8, p less than 0.001). Also, a further significant increase was observed when these macrophages were additionally incubated for 6 h with heterologous antibody-coated sheep red blood cells (range 1.2 - 1.57, p less than 0.001). Finally, the same studies were performed on a group of thalassemic patients with and without intrinsic iron overload. Again there were significant increases in monocyte ferritin content following culture as well as ingestion of heterologous sheep red cells, with magnitudes similar to those obtained with normal donor monocytes. Therefore we could not demonstrate the presence of a cellular ferritin synthesis defect in macrophages of thalassemic patients with intrinsic iron overload to explain the uncontrolled absorption of dietary iron from their gut.

Monocyte ferritin in idiopathic haemochromatosis, thalassaemia and liver disease.

Monocyte ferritin (MF) content was measured in normal subjects and patients with a variety of disorders of iron storage. MF was above the normal range in 4 patients with idiopathic haemochromatosis (IHC). However, in 4 patients with transfusion siderosis (TS), secondary to aplastic anaemia, who had similar elevations in serum ferritin, MF was highly elevated. 10 patients with thalassaemia intermedia and thalassaemia major with no previous history of transfusions, but with elevated serum ferritin, also had significantly elevated MF. Disproportionately low MF in IHC could reflect defective ferritin metabolism in reticuloendothelial cells in this disorder. Finally, in 3 patients with acute rises in serum ferritin caused by acute hepatitis, MF was not increased. This suggests that MF is not directly affected by high circulating levels of serum ferritin raised acutely, but rather reflects iron storage status in conditions not associated with primary disorders of iron metabolism.