Ferritin and Ferruginous Micelles in Normal Erythroblasts and Hypochromic Hypersiderernic Anemias

I N PREVIOUS PUBLICATIONS, we have shown that a part of the iron cycle may be studied by means of the electron microscope.’3 Actually, in the bone marrow of both humans and marnmifers the reticulum cells may be observed in the process of digesting the aged cells. Digestion continues for approximately 5 to 15 minutes as revealed by microcinematography by which the red cells may be seen immediately after ingestion divided into two or more parts in the cytoplasm.4 By electron microscopy, the different stages of digestion are easily followed. Generally, gradually extending vacuoles appear in the phagocytosed cells; sometimes hemolysis occurs in the cell cytoplasm where the remaining “ghost” is clearly seen. In both cases, the formation of a considerable quantity of small ferruginous granules around the red cell fragment is seen ( fig. 1). Under high-power magnification, these granules display the characteristic aspect of ferritin molecules. One of these molecules measures 50 A and is seen as four black specks situated in each of the four corners of a square.a It can thus be concluded that digestion of the red cells by reticulum cells in the marrow directly promotes the formation of ferritin molecules. These molecules are most frequently found in dusters visible in the optical microscope; they are known to histologists as hemosiderin. Among these clusters can be distinguished ferritin molecules and other substances not yet defined.6 Sometimes the hemosiderin clusters are crystalline in type, yielding pure ferritin ( fig. 2 ) . Ferritin and hemosidcrin observed in the reticular cells may originate from phagocytosis of the red cells or may simply be due to the storage, in ferritine form, of iron carried to the bone marrow by transferrin. Furthermore, the distribution of ferritin molecules to young erythroblasts by the reticulum cells can be studied. This occurs in the following manner: crythroblastic islands are present in the marrow bone, islands reported by the first cytologists but which now assume a new significance by means of electron microscopy.7 In the center of these islands are always found one or two reticulurn cells, which, charged with ferritin molecules in either a dispersed state or in the form of hemosiderin clusters, give up these molecules to the erythroblasts by a phenomenon closely related to pinocytosis1 and which may be termed ropheocytosis.8 This phenomenon is quite constant in normal conditions and in numerous diseases. Nevertheless, it is not known whether all the iron required for hemoglobin formation enters by pinocytosis or whether a part of it reaches the red cell directly from the plasma transferrin. Otherwise, it may be surmised that several mechanisms play a simultaneous role: