Rabbit bone marrow after administration of saponin. An electron microscopic study

Saponin rapidly induced injury to the wall of vascular sinuses in rabbit bone marrow so that the barrier between hematopoietic cells and the circulation became defective. This change was followed by hypocellularity and necrosis and fibrosis. Adult male rabbits received saponin intravenously (2 mg. per kg.) every 4 days for periods of up to 4 weeks; the animals were killed at varied times. In untreated animals, much of the sinus wall consisted only of endothelium. Within 2 hours after administration of saponin the endothelium was damaged and hematopoietic cells, mostly reticulocytes and normoblasts, entered the circulation. Some sinuses hemorrhaged into the hematopoietic compartment. At 4 hours, sinuses were markedly dilated and hemorrhage was extensive. By 3 days, extravasated erythrocytes, which were tending to aggregate, were unevenly distributed in the extravascular space of marrow. Damaged hematopoietic cells were dispersed among them. Regenerating blood vessels were noted and a few clusters of hematopoietic cells occurred in association with fibroblasts. At 1 week, a large portion of the marrow was either necrotic or contained large-scale diffuse or focal hemorrhage. Fibrotic areas often surrounded the arteries. After 2 to 4 weeks, myelofibrosis became pronounced. The fibrotic tissue was well vascularized and contained small clusters of hematopoietic cells and a few fat cells. Macrophages were abundant and tended to fuse, forming multinucleated giant cells surrounding pockets of degenerated fat cells.