Stimulation of normal erythropoiesis in vitro by macrophages from erythroleukemic mice

The erythroleukemia induced in mice by the Friend virus complex is caused to regress by macrophages. To determine whether the effect of macrophages on leukemia is due to their role in the regulation of erythropoiesis, investigators examined the influence of macrophages from normal and leukemic mice on in vitro colony formation by erythroid progenitor cells [colony-forming units of erythroid progenitor cells (CFU-E)]. Plasma clot cultures of CFU-E were grown over monolayers of macrophages separated from the CFU-E cultures by a layer of agar. Macrophages from progressors (those leukemic mice that will not undergo leukemia regression) significantly stimulated CFU-E, whereas macrophages from regressors (those that will undergo leukemia regression) had no effect on colony formation. Monolayers of normal resident macrophages did not affect in vitro erythropoiesis, while less mature macrophages (peripheral blood mononuclear cells) or nonspecifically activated macrophages (exudate induced) in monolayer stimulated CFU-E. Stimulation by macrophages from leukemic mice was dependent on the presence of virus-producing cells. CFU-E from erythroleukemic mice were resistant to stimulation by leukemic macrophages. These results demonstrated that macrophages from progressively leukemic mice influenced normal colony formation of CFU-E in vitro and that these effects could be related to the ability of macrophages to cause leukemia regression.