B-lymphocyte-derived burst-promoting activity is a pleiotropic erythroid colony-stimulating factor, E-CSF.
Human B-lymphocyte-derived erythroid burst-promoting activity (B-BPA) is a pleiotropic, lineage-specific regulator of erythropoiesis. Our present data indicate that B-BPA plays an important role as an erythroid colony-stimulating factor (E-CSF) in modulating progenitor growth and differentiation throughout erythropoiesis. E-CSF has discrete effects on both early (erythroid burst-forming units, BFU-E) and late (erythroid colony-forming units, CFU-E) progenitors from normal bone marrow. In serum-substituted fibrin clot cultures, E-CSF stimulates the proliferation of BFU-E, resulting in an increase in the number of erythroid bursts over a wide range of erythropoietin (Epo) concentrations. We now have shown that E-CSF also acts on CFU-E by increasing their sensitivity to Epo markedly, resulting in a tenfold left-shift in the Epo dose-response curve. Using purified target-cell populations of human and murine erythroleukemia cells that are Epo-independent for growth, we have found that E-CSF stimulates cell proliferation directly, increasing the plating efficiency of these cells in suspension culture by 50%-165%. B-BPA also increased proliferation of these cells in semi-solid medium. Importantly, the combination of E-CSF and Epo resulted in a profound increase in the growth and maturation of the resultant colonies. Therefore, the data indicate that E-CSF can regulate the growth of cells independently of added Epo and, in addition, can synergize with Epo in regulating the growth and differentiation of erythroid progenitors.
Feldman
L
L
Laboratory for Cell and Molecular Biology, New England Deaconess Hospital, Boston, MA 02215.
Frazier
J G
JG
Sytkowski
A J
AJ
D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry* / Q000187:drug effects; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002848:Chromatography, DEAE-Cellulose; D003115:Colony-Stimulating Factors / Q000032:analysis* / Q000494:pharmacology / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008222:Lymphokines / Q000032:analysis* / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D017077:Culture Media, Conditioned; D008222:Lymphokines; D019714:Tissue Inhibitor of Metalloproteinases; D004921:Erythropoietin