Effect of postirradiation bleeding or endotoxin on proliferation and differentiation of hematopoietic stem cells

Abstract Bleeding after irradiation failed to affect the time of onset or rate of regeneration of the hematopoietic stem cell compartment as measured by a split-dose irradiation method. Bleeding after a single 600 rad exposure hastened the time of onset of erythropoiesis as measured by spleen colonies and 59Fe uptake, but the early rise was abortive and the second increase began at the same time as the first increase seen in irradiated controls. The largest abortive increase was seen when bleeding occurred within 4 hr of irradiation. Lesser effects were seen when bleeding occurred 12 or 24 hr after and no effect 48 hr after irradiation. A generation time of 6.4 hr for a colony-forming cell that forms a colony in 4 days was calculated from the estimated number of cells in one such colony. Injection of cytosine arabinoside at the time of bleeding reduced colony numbers and 59Fe uptake equally in bled and control mice. Injection of 25 µg Salmonella typhosa endotoxin just after irradiation produced a similar early abortive rise in microscopic granulocytic colonies. These results are compatible with a model for pluripotential stem cell compartment in which: (1) differentiation and self-replication occur concomitantly unless the compartment is reduced below approximately 1O% of normal size; then self-replication occurs without appreciable differentiation; (2) for a short time (∼ 24 hr) after depletion below the threshold, differentiation can occur in response to strong stimuli.