The clonal proliferation of normal mouse hematopoietic cells: enhancement and suppression by colony-stimulating factor combinations.

Combinations of relatively high concentrations of the four colony-stimulating factors (CSFs) in cultures of normal mouse bone marrow cells stimulated subadditive responses in the number of colonies developing but, with some combinations, superadditive increases in mean cell numbers per colony. This latter effect was due largely to the induced development of small numbers of giant colonies containing macrophages with or without granulocytes. However, in cultures including a combination of granulocyte-macrophage-CSF (GM-CSF) with macrophage-CSF (M-CSF), a selective reduction in the number of pure macrophage colonies was observed together with a change in the morphology of those colonies that did develop. Recloning studies on macrophage colonies showed that the inhibitory action of the GM-CSF plus M-CSF combination was a direct one on the colony cells. The example of inhibition observed suggests that combined stimulation by two positive growth factors can sometimes result in a selective reduction of the production of certain cells, a possibility needing further exploration.