Reactivation of HbF synthesis in normal adult erythroid bursts by IL-3.
Reactivation of HbF synthesis has been reported in normal adult erythroblast colonies ('burst') generated by erythroid progenitors (BFU-E) after seeding peripheral blood mononuclear cells (PBMC) in fetal calf serum-supplemented (FCS+) semisolid cultures stimulated by erythropoietin (Ep). Reactivation is almost totally suppressed when: (i) PMBC are grown in optimized FCS- culture or (ii) PBMC are first stringently depleted of monocytes and then plated in FCS+ medium (i.e. BFU-E growth in FCS+Mo- culture). In either case, addition of biosynthetic granulocyte-macrophage colony stimulating factor (GM-CSF) induces a dose-related increase of relative HbF synthesis up to the level in FCS+ culture. We report that, in FCS- culture of partially purified adult blood BFU-E, treatment with biosynthetic interleukin 3 (IL-3) causes a dose-related rise of relative HbF production in the bursts. A similar phenomenon is observed in FCS+ culture of highly purified BFU-E. The rise of HbF synthesis is seemingly mediated, at least in part, by a direct effect of IL-3 at BFU-E level. It is tentatively concluded that reactivation of HbF in vitro, as well as in a variety of in vivo conditions (i.e. stress erythropoiesis, marrow regeneration), may be at least in part mediated by IL-3 and GM-CSF.
Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, Italy.
M
M
Gabbianelli
E
E
Pelosi
C
C
Labbaye
M
M
Valtieri
U
U
Testa
C
C
Peschle
D000328:Adult; D001769:Blood; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007525:Isoelectric Focusing
D003470:Culture Media; D007377:Interleukin-3; D005319:Fetal Hemoglobin