The clonal proliferation of normal mouse hematopoietic cells: enhancement
and suppression by colony-stimulating factor combinations
D Metcalf and NA Nicola
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne
Hospital, Victoria, Australia.
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.
Volume 79,
Issue 11,
pp. 2861-2866,
06/01/1992
Copyright © 1992 by The American Society of Hematology