Sources and nature of granulocyte-macrophage colony stimulating factor in fetal mice.

At the earliest stages of fetal hepatic hemopoiesis in CBA mice (11-12 days gestation), colony stimulating activity could be found only in peripheral blood, yolk-sac fluid and media conditioned by yolk-sacs (YSCM). The colony stimulating factor (GM-CSF) from YSCM was able to be concentrated by absorption to DEAE-cellulose and subsequent elution. Titration of this material produced a sigmoid dose-response curve in agar cultures of adult CBA bone marrow cells. Unlike the high proportion of granulocyte colonies stimulated by the GM-CSF from mouse lung conditioned medium, all concentrations of YSCM produced a high proportion of macrophage colonies after 7 days of incubation. Mixing experiments eliminated the possibility that a specific inhibitor preventing granulocyte differentiation was present in YSCM. Fetal liver cells were relatively unresponsive to YSCM, but their ability to respond increased with gestational age. When stimulated by YSCM, fetal liver colony forming cells from mice of all gestational ages produced more than 90% macrophage colonies after 7 days of incubation. The experimental data suggest that the proliferation and differentiation of granulocyte and macrophage precursors in the early fetal liver could be controlled by a fetal type of GM-CSF favoring macrophage production.