A study of hemosiderosis with the aid of electron microscopy; with observations on the relationship between hemosiderin and ferritin

Abstract

Hemosiderin deposits in rats and in man were studied and compared by means of electron and light microscopy. Typical, isotropic, iron-positive hemosiderin granules were found to contain innumerable, closely packed, electron-dense particles, embedded in matter that was much less dense to electrons. Similar dense particles were often scattered diffusely through the cytoplasmic matrix of cells containing hemosiderin granules. In cells of proximal convoluted tubules of rats given repeated intraperitoneal injections of hemoglobin the hemosiderin granules contained dense particles with a mean diameter of 55 A, and with a size-frequency distribution that indicated uniformity. These particles corresponded in size to the iron micelles of ferritin molecules. There was less uniformity of particles in hemosiderin granules situated in liver and reticulo-endothelial cells of rats that had been given a diet containing ethionine. The dense aggregates representing hemosiderin granules were often situated inside discrete cytoplasmic organelles that were bordered by membranes, and sometimes contained "cristae"; and often the membranous borders were markedly disrupted. The term "sidersomes" is proposed for these specialized cytoplasmic structures which may be derivatives of mitochondria, and apparently play a part in the formation of hemosiderin. Ferritin was crystallized from the livers and kidneys of the hemosiderotic rats with ease, but could not be crystallized from comparable quantities of liver and kidney tissue of untreated control rats. Specimens from the liver and spleen of a patient with advanced hemosiderosis, obtained at an operation, were also studied. In liver and reticulo-endothelial cells many particles with diameters of about 60 A were scattered through the cytoplasmic matrix. By contrast, hemosiderin granules in the same cells contained particles that varied considerably in size. In representative granules, examined at high resolution, the size-frequency distribution of particle diameters displayed a periodicity consistent with the presence of small, uniform subunits. Electron micrographs of ferritin, isolated from the spleen of the same patient, provided confirmation for the inferences that the dense particles observed inside cells are iron micelles, and that ferritin is probably a component of hemosiderin.