The Cellular Transformation of Injected Colloidal Iron Complexes Into Ferritin and Hemosiderin in Experimental Animals

Abstract

Although there have been numerous studies on the fate of injected iron compounds in experimental animals (1-8), the transformation of the iron compounds within individual cells has not yet been traced at the molecular level. Recent work in which electron microscopy was combined with other techniques (9-12) has provided information on the molecular structure and the disposition of hemosiderin in several types of cells under varying circumstances, on the relationship of hemosiderin to ferritin, and on the possible role of specialized mitochondria ("siderosomes") in hemosiderosis. In the work now to be presented it has proved possible to distinguish intracellular deposits of iron compounds, given parenterally, from ferritin and from indigenous hemosiderin, and to gain insight into the transformation of the injected iron compounds into ferritin and hemosiderin. The findings bear on several aspects of iron metabolism, especially on the utilization of colloidal iron preparations within macrophages and endothelial cells. General Plan of ExperimentsThe general plan of the experiments was, first, to trace the sequence of changes in the fine structure of intracellular deposits of injected iron compounds in several types of cells in mice and rats at various intervals following intraperitoneal injection; second, to compare the physico-chemical nature of the intracellular material with that of the iron compounds prior to their injection; tkirdly, to confirm the actual presence of ferritin, about or in relation to deposits

Role of iron in Trypanosoma cruzi infection of mice.

“…It had thus been determined that T. cruzi provoked a hypoferremic response, presumably by intracellular sequestration of iron within the RES (4,5). Furthermore, it was observed that iron-dextran, which preferentially delivers iron to the intracellular RES stores (13), enhanced the pathogenicity of T. cruzi infection. Hence, it was of interest to determine the effects of reduction of intracellular iron stores on the course of infection with T. cruzi.…”

“…Furthermore, iron-dextran specifically produces an increase in the intracellular RES iron levels (13), whereas desferrioxamine B specifically chelates and removes intracellular iron rather than the iron bound to transferrin (14). Thus, desferrioxamine B and an iron-deficient diet protected against intracellular T. cruzi by a reduction in the intracellular iron stores, whereas iron-dextran produced a detrimental effect by augmenting intracellular iron stores.…”

Observations on Subcutaneous Macrophages. Phagocytosis of Iron‐dextran and Ferritin Synthesis

“…At first individual molecules of ferritin are uniformly distributed throughout the cytoplasm, accompanied by a few molecules in the nucleoplasm but, as a rule, none in mitochondria. One week after injection, vacuoles containing a mixture of iron-dextran and ferritin are found, and these are gradually replaced by vacuoles containing only ferritin.COLLOIDAL iron preparations contain macromolecular particles which can be distinguished in electron micrographs from the images produced by the ferric hydroxide micelles of the iron-storage protein, ferritin [Richter, 1959;Bessis and Breton-Gorius, 1959;Muir, 1960]. Thus it is possible to observe the cellular transformation of administered iron preparations into ferritin and haemosiderin.…”

A morphological study of ferritin synthesis in macrophages with ingested ferric hydroxide-potassium polyvinyl sulfate complexes.

“…Heavy deposition of ferritin is induced easily in animals by injecting them with and excess of iron compounds (12,19,20). Thus, the process of ferritin formation can be analyzed by using animal cells loaded with iron.…”