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Interacting cytokines regulate in vitro human megakaryocytopoiesis
E Bruno, ME Miller and R Hoffman
Department of Medicine, Indiana University School of Medicine, Indianapolis
46223.
The effects of hematopoietic growth factors on in vitro human
megakaryocytopoiesis were studied using a serum-depleted culture system.
Both recombinant interleukin-3 (r-IL-3) and recombinant
granulocyte-macrophage colony-stimulating factor (rGM-CSF) increased
megakaryocyte (MK) colony formation (P less than .01) above that observed
in baseline cultures. Recombinant interleukin-4 (rIL-4) and interleukin 1
alpha (rIL-1 alpha) failed either to promote MK colony formation alone or
to increase rIL-3 or rGM-CSF promoted colony formation. Recombinant
erythropoietin (rEpo) and purified thrombocytopoiesis-stimulating factor
(TSF) did not increase (P greater than .05) MK colony formation when added
alone but synergized with rIL- 1 alpha, leading to a twofold increase in MK
colony formation. Such a synergistic relationship was not observed between
rIL-4 and rEpo. In addition, TSF enhanced the ability of rIL-3 but not
rGM-CSF to promote MK colony formation. Addition of rEpo to optimal or
suboptimal concentrations of rGM-CSF or suboptimal concentrations of rIL-3
resulted in a significant increase (P less than .05) in the total number of
MK-containing colonies, due to the appearance of multilineage colonies
containing MKs. The addition of rEpo to optimal concentrations of rIL-3
resulted in increased numbers of multilineage colonies containing MKs;
however, the number of total MK-containing colonies was not significantly
increased when compared to assays containing rIL-3 alone. By contrast,
transforming growth factor-beta (TGF-beta) inhibited both rIL-3, and
rGM-CSF promoted MK colony formation, with optimal inhibition resulting in
a 35%-45% reduction of MK colony formation.(ABSTRACT TRUNCATED AT 250
WORDS)
Volume 73,
Issue 3,
pp. 671-677,
02/15/1989
Copyright © 1989 by The American Society of Hematology
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