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Stem cell factor in combination with granulocyte colony-stimulating factor
(CSF) or granulocyte-macrophage CSF synergistically increases
granulopoiesis in vivo
TR Ulich, J del Castillo, IK McNiece, ES Yi, CP Alzona, SM Yin and KM Zsebo
Department of Pathology, University of California, School of Medicine,
Irvine 92717.
Recombinant rat stem cell factor (rrSCF) and recombinant human granulocyte
colony-stimulating factor (G-CSF) coinjected for 1 week in rats cause a
synergistic increase in mature marrow neutrophils accompanied by a striking
decrease in erythroid and lymphoid marrow elements. The spleens of the same
rats show increased granulopoiesis as well as increased erythropoiesis as
compared with the spleens of rats treated with either growth factor alone.
Splenic extramedullary erythropoiesis may act to compensate for the
decrease in marrow erythropoiesis. The coinjection of rrSCF and G-CSF
causes an increase in marrow mast cells at the end of 1 week, but the
increase is much less than in rrSCF-alone-treated rats. The combination of
rrSCF and G- CSF increases the rate of release of marrow neutrophils into
the circulation and causes a dramatic synergistic peripheral neutrophilia,
beginning especially after 4 days of treatment. Colony-forming assays of
all experimental groups showed a synergistic increase in colony- forming
unit granulocyte-macrophage (CFU-GM) in the marrow, but not in peripheral
blood, after coincubation with SCF plus granulocyte- macrophage CSF
(GM-CSF) as opposed to GM-CSF alone, showing anatomic compartmentalization
between a more primitive marrow CFU-GM subset and a more mature peripheral
blood CFU-GM subset. In vivo daily administration of SCF plus GM-CSF
results in a synergistic increase in marrow neutrophils, but not the
striking synergistic increase in circulating neutrophils that is observed
with SCF plus G-CSF.
Volume 78,
Issue 8,
pp. 1954-1962,
10/15/1991
Copyright © 1991 by The American Society of Hematology
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