Stimulation of neutrophil production in CSF-1-responsive clones
G Rothstein, SM Rhondeau, CA Peters, RD Christensen, D Lynch and S Gillis
Division of Human Development and Aging, University of Utah School of
Medicine, Salt Lake City 84132.
The hematopoietic growth factor CSF-1 has been considered relatively
lineage specific for the production of macrophages, whereas GM-CSF elicits
a predominance of neutrophils. It is likely that in vivo, individual clones
are stimulated by the two CSFs, although the effect of dual stimulation on
progenitors and their progeny has not been completely explored. We found
that in cultures initiated with low concentrations of CSF-1 or GM-CSF,
alone or in combination, production of macrophages predominated. Maximally
stimulatory concentrations of CSF-1 elicited a predominance of macrophages,
whereas maximal GM-CSF elicited many more neutrophil/macrophage colonies
and pure neutrophil colonies. A combination of maximal CSF-1 and GM-CSF
elicited the same differentiation as GM-CSF alone. Delayed addition of
GM-CSF to cultures initiated with CSF-1 elicited colonies indistinguishable
from GM-CSF alone, suggesting that neutrophil production had been switched
on by GM- CSF. In mapping studies, colonies initiated by CSF-1 increased or
switched on neutrophil production when GM-CSF was added as a second
stimulus. These studies show that individual clones are responsive to both
CSFs, and that the differentiating influence of GM-CSF predominates over
that of CSF-1. In cultures to which only CSF-1 was added, a population of
progenitors was sustained that produced neutrophils only after a GM-CSF
stimulus. Thus, CSF-1 may participate in maintaining a reserve of
progenitors for neutrophils during periods of increased neutrophil demand.
Volume 72,
Issue 3,
pp. 898-902,
09/01/1988
Copyright © 1988 by The American Society of Hematology
