TY - JOUR
T1 - Influence of recombinant hematopoietins and of fetal bovine serum on the globin synthetic pattern of human BFUe
AU - Migliaccio, A. R.
AU - Migliaccio, G.
AU - Brice, M.
AU - Constantoulakis, P.
AU - Stamatoyannopoulos, G.
AU - Papayannopoulou, T.
PY - 1990
Y1 - 1990
N2 - 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 cultured 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) γ-globin and γ-globin mRNA levels. Reduced γ-globin in serum-deprived cultures was also reflected by a smaller proportion of erythroblasts with detectable γ-globin by immunofluorescence. Erythroid bursts induced by either GM-CSF or IL-3 produced similar levels of γ-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.
AB - 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 cultured 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) γ-globin and γ-globin mRNA levels. Reduced γ-globin in serum-deprived cultures was also reflected by a smaller proportion of erythroblasts with detectable γ-globin by immunofluorescence. Erythroid bursts induced by either GM-CSF or IL-3 produced similar levels of γ-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.
UR - http://www.scopus.com/inward/record.url?scp=0025159851&partnerID=8YFLogxK
U2 - 10.1182/blood.v76.6.1150.1150
DO - 10.1182/blood.v76.6.1150.1150
M3 - Article
C2 - 1698099
AN - SCOPUS:0025159851
VL - 76
SP - 1150
EP - 1157
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -