Erythropoietic precursors in mice under erythropoietic stimulation and suppression.

Using a methylcellulose clonal cell culture technique, we examined serial changes in erythropoietic precursors in the femur, spleen, and blood of mice prepared with bleeding, erythropoietin injections, or hypertransfusion with packed red blood cells. Significant changes were observed for all hemopoietic organs in the number of erythropoietic burst-forming units (BFU-E) and erythrocytic colony-forming units (CFU-E). In mice prepared with bleeding or erythropoietin injections, the serial changes of BFU-E and CFU-E were similar to but less striking than those seen in mice with phenylhydrazine-induced anemia. The transient decline in the femoral BFU-E coincided with the temporary increase in the splenic and blood BFU-E. A more pronounced increase in CFU-E was noted in the femur and spleen of these mice. In hypertransfused mice, the direction of the changers in the erythropoietic precursors was opposite. While femoral BFU-E increased mildly, a significant drop was noted in the splenic and blood BFU-E. Both femoral and splenic CFU-E declined and remained low while erythrocytosis presisted. Next, we examined the proliferative state of the erythropoietic precursors in the marrow and spleen using short-term incubation with high specific tritiated thymidine. In the marrow and spleen of normal mice, the BFU-E and CFU-E in the DNA synthetic phase was about 36 and 74%, respectively. Neither induction of anemia with phenylhydrazine hydrochloride nor polycythemia with hypertransfusion caused changes in the proliferative state of the precursors. These results indicate that the serial changes in the number of BFU-E represent migration of BFU-E from marrow to spleen rather than BFU-E proliferation. Marrow CFU-E increased in anemic mice and decreased in polycythemic mice without changes in their proliferative state. It is possible that the target of erythropoietic stimulation in mice may be cells at maturational stages intermediate between BFU-E and CFU-E.