An electron microscopic study of red bone marrow.

The different cell types of bone marrow have been characterized in terms of what may be seen in ultrathin sections with the electron microscope. The cytologic details clearly visible under these circumstances include specific granules, mitochondria, RNA granules, endoplasmic reticulum, amorphous cytoplasmic material and nucleoli. After experience with well-fixed material one is rarely in doubt about how to classify any given cell. Variations in these criteria can be compared and provide additional information for tracing cell relationships. A full range of intermediates has been found establishing the derivation of neutrophil, eosinophil and erythrocyte from a common ancestral myeloblast. The origin of the other cell types has not been traced in comparable detail. The specific granules of the different granulocytes have been described. Of considerable curiosity is the eosinophilic granule which consists of a disc of dense homogeneous material enclosed in a spheroidal mass of lower density, but similar homogeneity. Basophilic granules appear to be made up of stacked, irregular lamellae. But there is some reason for believing that a water-soluble component may have been extracted from these. Neutrophil granules are of two main types. A homogeneous granule of low density is the predominant type in late development, but a larger osmiophilic granule that appears to be formed within a vacuole is characteristic of early stages of specialization. Amorphous material of substantial density (presumably hemoglobin) becomes a feature of the cytoplasm of erythroblasts and normoblasts. Large and well defined nucleolar masses are conspicuous characters of the myeloblast and reticular cell, but disappear from the other cell lines as they specialize. Unusually large and very watery mitochondria are specific features of the myeloblast and reticular cell. The mitochondria apparently condense as cell specialization occurs in all other cell lines except the basophil. The endoplasmic reticulum develops greatly during the neutrophilic and eosinophilic promyelocyte stage and then regresses, except for an unusually spectacular development of this system in the rat (but not the guinea pig) eosinophilic myelocyte. The system is notable also in the megakaryocyte, and particularly so in the plasma cell. There are only small variations recognizable in the RNA granule dispersion of the various cell types. The extrusion of the normoblast nucleus to form an erythrocyte, and a surviving nucleus covered by an excessively thin rim of cytoplasm, has been observed occasionally. Subsequent changes in the nuclear mass suggest that degenerative changes then occur rapidly, but the later phases of this have not been identified. Platelet cytoplasm has been compared with that of megakaryocytes. It is thought to be identical. Besides specific granules, it sometimes contains mitochondria and endoplasmic reticulum. The manner in which platelets are formed from megakaryocytes is discussed. A white thrombus is illustrated and discussed. Isolated reticular cells are rare or nonexistent in hyperplastic marrow. So also are isolated reticular fibers. A few fibers occur with the reticuloendothelial lining of sinusoids, and more with larger vessels. Hypoplastic marrow which might show more reticular cells has not been studied for comparison. Lymphocytes and monocytes have been observed, but a full discussion of these cells is postponed until lymphoid tissues have been studied. Considerable attention has been given to the character of the sinusoidal lining. The reticuloendothelial cells have long protoplasmic processes which outline the wall structure, but which do not begin to make a complete wall covering. Cells of most juvenile types may be nakedly exposed to the circulating blood, and even bulge far into the lumen. The circulation is thus fundamentally open in character. Intersinusoidal capillaries as defined by Doan, Cunningham and Sabin 9 do not exist in this active mammalian red marrow. Studies of hypoplastic marrow unfortunately are not available for comparison. Erythropoiesis occurs in extravascular spaces along with granulopoiesis.