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At least 19 recordsLinked to original sources
PubMed1957

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

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.

Animals↗
PubMed1960

The nature of storage iron in idiopathic hemochromatosis and in hemosiderosis. Electron optical, chemical, and serologic studies on isolated hemosiderin granules.

Using three different methods of cells fractionation, hemosiderin granules were isolated from tissues (liver and/or spleen) of three patients. The samples were obtained from a case of idiopathic hemochromatosis, a case of thalassemia major with secondary (transfusional?) hemosiderosis, and a case of transfusional hemosiderosis associated with an unclassified anemia. Iron, nitrogen, and protein content of the hemosiderin granules varied over a wide range. Electron microscopy of sectioned granules revealed aggregates of dense particles of different shapes, with diameters ranging from 10 A to about 75 A. In some of the granules dense particles corresponding to the iron hydroxide micelles of ferritin molecules were abundant. But many of the granules contained very few of these molecules. The presence of ferritin and apoferritin in the samples of hemosiderin granules was demonstrated by means of precipitin tests in agar-gel, using rabbit antiferritin sera with known antibody nitrogen concentrations. At least three antigenic components were detected in highly purified crystalline ferritin prepared from tissues of the three patients; the hemosiderin granules contained the same antigens, but probably in much smaller quantities. Both ferritin and apoferritin molecules were extracted from hemosiderin granules, and were demonstrated in the electron microscope after suitable preparation. The solubility curve of human ferritin in solutions of (NH(4))(2)SO(4) was investigated. The results indicate that substantial quantities of ferritin or apoferritin can be lost in saline, aqueous media during isolation of hemosiderin granules from cells. It was shown by means of electron microdiffraction on selected hemosiderin granules that the dense particles represent forms of partly hydrated alpha-Fe(2)O(3). The conditions necessary for electron microdiffraction in an electron microscope precluded an exact determination of the state of hydration of the alpha-Fe(2)O(3) or of its structural relation to (FeOOH) micelles of pure ferritin in its undenatured state. The findings were considered in the light of evidence on the structure and disposition of hemosiderin in situ in cells, and on the structure of ferritin. Differences between endogenous hemosiderin and hemosiderin derived from injections of colloidal iron compounds were pointed out. The evidence indicates that in hemochromatosis and in secondary hemosiderosis much of the inorganic storage iron in liver and spleen is derived from degraded ferritin. The findings suggest that an abnormal cellular metabolic pathway of ferritin is implicated in the pathogenesis of hemochromatosis and transfusional hemosiderosis.

Anemia↗