Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones.
In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte-macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum.
Christensen
R D
RD
Division of Human Development and Aging, University of Utah School of Medicine, Salt Lake City 84132.
Koenig
J M
JM
Viskochil
D H
DH
Rothstein
G
G
D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D005333:Fetus; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D014316:Tritium; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013936:Thymidine