1. The effect produced by the intravenous administration of collargol on the bone marrow of rabbits varies directly with the amount of collargol injected, and three fairly well defined stages could be recognized. (a) An initial stage after comparatively few and small doses, with erythrocytic and endothelial hyperplasia in the bone marrow and with evidences of this stimulation in the peripheral blood in the form of young erythrocytes and normoblasts. (b) An intermediary stage which followed the injection of larger amounts of collargol, and which was characterized by a predominant myeloid hyperplasia. (c) A final stage with marked bone marrow aplasia and with colloidal silver deposited in endothelial cells, as well as in clasmatocytes. This was associated with a high grade anemia with low color index, resembling aplastic anemia in its main features. This stage terminated fatally. 2. There was no evidence of injury to blood cells in the peripheral circulation. The erythrocytic bone marrow aplasia was present before any appreciable decrease of red blood cells was found in the peripheral blood. 3. The results were less clear-cut in a series of rats, but anemia of a similar type was produced in all animals when sufficiently large doses were injected. 4. Splenectomy did not alter the course in rats materially. 5. It is fair to conclude that the cause of the anemia produced may be sought in the deviation of the parental endothelial cell toward clasmatocyte formation at the expense of the development of erythrocytes. 6. It is suggested that the results may be offered in support of the theory of the endothelial origin of both clasmatocytes and red blood cells.
In the study, both experimental and clinical, of the hematopoietie system, attention has been directed almost exclusively to the peripheral blood. This is due to the ease with which the peripheral blood may be examined and the difficulties encountered when attempts are made to analyze the bone marrow and interpret the results obtained. The recent work of Sabin, Doan, and Cunningham (1-3), however, on the structure and function of the bone marrow has greatly facilitated the study of the hematopoietic organs. The theory of these authors as to the origin of red blood cells and clasmatocytes from the endothelium lining the sinuses of the bone marrow, furnishes a working hypothesis for the study of the function of the bone marrow, and its reaction to external influences.In a series of investigations on bone marrow reactions the hypothesis of the endothelial origin of the red blood cells and the cla~matocytes has been used as aworking basis. In a former study (4, a) it was found that a colloidal suspension of a heavy metal (collargol) produced an aplastic anemia, interpreted as due to injury to the endothelial cells of the hematopoietic organs. In a control experiment (4,b) with a colloidal suspension of carbon particles in the form of drawing ink, the results warranted the conclusion that carbon particles as such stimulate phagocytosis, but do not inhibit, to any appreciable extent, the formation of erythrocytes. This seems to indicate that the particles ingested by the phagocytic cells must exert a toxic action if they 753 on
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