The role of the blood island during normal and 5-fluorouracil-perturbed hemopoiesis.

The blood island is found in all hemopoietic organs. It consists of a central macrophage surrounded by other hemopoietic cells, notably developing erythroblasts and cells of the myeloid lineage. In this report, several lines of investigation are combined to discuss the role of the erythroblastic island in erythropoietic differentiation and to question the source and role of circulating erythropoietin (epo). In both cultured and fresh normal bone marrow macrophages, we demonstrate epo gene expression and, simultaneously, localize epo intracellularly. The following observations have also been made: a) red cell production initiated in vitro in mouse fetal liver and normal bone marrow cell suspensions by the addition of horse serum usually occurs in the presence of macrophages that form the blood island functional unit; however, epo can only be detected in the fetal liver supernatants and not in the supernatants derived from bone marrow cultures; b) in 5-fluorouracil-treated mice, circulating epo levels, measured immunologically by ELISA, RIA, and biologically by the in vitro stimulation of mouse bone marrow CFU-E, converged between days 10 and 12 to give epo concentrations that did not correspond with the degree of anemia; c) when bone marrow cells from day 5, 5-fluorouracil-treated mice are placed in culture for 24 hours, an active erythropoiesis is observed in which developing and mature erythrocytes surround macrophages expressing the epo gene (blood islands); at this time immunologically active epo (but little biologically active epo) is present. After 14 days in culture, no erythropoiesis is observed and the culture consists of macrophages, some of which are expressing the epo gene, and biologically, rather than immunologically, active epo is present. These results show that the blood island is a necessary functional unit for active erythropoiesis.