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Influence of recombinant hematopoietins and of fetal bovine serum on the
globin synthetic pattern of human BFUe
AR Migliaccio, G Migliaccio, M Brice, P Constantoulakis, G Stamatoyannopoulos and T Papayannopoulou
Department of Medicine, University of Washington, Seattle 98195.
We have studied the effects of recombinant hematopoietic growth factors,
granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or
interleukin-3 (IL-3) on the globin program of adult human erythroid
progenitors (BFUe) stimulated to terminal differentiation by erythropoietin
under fetal bovine serum (FBS)-supplemented or FBS- deprived culture
conditions. Fetal globin production by BFUe-derived erythroblasts was
assessed at the protein and mRNA level and its cellular distribution was
evaluated by immunofluorescence. Although hemoglobinization and maturation
of BFUe-derived erythroblasts was by and large comparable in FBS-replete
versus FBS-deprived cultures, the latter had significantly less (up to
20-fold) gamma-globin and gamma- globin mRNA levels. Reduced gamma-globin
in serum-deprived cultures was also reflected by a smaller proportion of
erythroblasts with detectable gamma-globin by immunofluorescence. Erythroid
bursts induced by either GM-CSF or IL-3 produced similar levels of
gamma-globin both in FBS- supplemented and in FBS-deprived cultures. These
results, obtained even in cultures of highly enriched BFUe, suggest that
GM-CSF and IL-3, although they significantly increase the number and size
of erythroid bursts, do not by themselves exert a direct influence on the
level of fetal globin synthesis. By contrast, factor(s) present in FBS
appear to exert a dominant influence on fetal globin synthesis in vitro.
Although FBS-deprived conditions appear to largely abrogate the in vitro
activation of fetal hemoglobin (Hb F) in normal samples, they do support
increased Hb F production in samples from patients with hereditary
persistence of fetal hemoglobin or from cord blood.
Volume 76,
Issue 6,
pp. 1150-1157,
09/15/1990
Copyright © 1990 by The American Society of Hematology
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