Stimulation of murine colony-forming cells with high proliferative
potential by the combination of GM-CSF and CSF-1
IK McNiece, BE Robinson and PJ Quesenberry
University of Virginia, School of Medicine, Charlottesville 22908.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously
been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages
to act as an erythroid burst-promoting activity and to stimulate limited
replication of spleen colony-forming cells. Here we demonstrate that murine
GM-CSF alone or in combination with macrophage colony-stimulating factor
(CSF-1) can stimulate colony- forming cells in bone marrow (BM) that have a
high proliferative capacity. In cultures of BM from mice treated with
5-fluorouracil (FU) eight days before sampling, GM-CSF alone or in
combination with CSF-1 stimulated the formation of large macrophage
colonies with diameters greater than 0.5 mm. CSF-1 alone, at 800 units or
greater, also stimulated larger colonies; however, these colonies were
always less than 1.1 mm in diameter, whereas GM-CSF in combination with
CSF-1 stimulated many colonies with diameters between 1 and 4 mm. At all
doses of CSF-1 tested, the combination of factors resulted in a synergistic
increase in colonies with diameters greater than 1.0 or 2.0 mm. Analysis of
the incidence of colony-forming cells in the BM of normal mice and mice 2,
4, 6, and 8 days after FU treatment demonstrated that the progenitor cells
stimulated by GM-CSF alone or in combination with CSF-1 were depleted by FU
treatment in vivo and regenerated more rapidly than did the macrophage
progenitors (M-CFC) stimulated by CSF-1 alone. This is similar to the
properties of the previously described high-proliferative potential,
colony-forming cell (HPP-CFC) that is responsive to interleukin-3 plus
CSF-1 but not the HPP-CFC stimulated by hematopoietin 1 plus CSF-1. These
data suggest that GM-CSF plus CSF-1 act synergistically to stimulate a
population of progenitor cells that have a high proliferative potential and
have properties similar to those of the population of HPP-CFC stimulated by
interleukin-3 plus CSF-1.
Volume 72,
Issue 1,
pp. 191-195,
07/01/1988
Copyright © 1988 by The American Society of Hematology
