Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood.
The proliferative effects of recombinant human interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in semi-solid and liquid cultures of purified CD34+ hematopoietic cells obtained from umbilical cord blood. No important differences in overall cloning efficiencies in response to IL-3 or GM-CSF were observed in semi-solid medium in the presence of erythropoietin (Ep). However, GM-CSF was less effective for the development of erythroid bursts (BFU-E), and only IL-3 was observed to induce significant numbers of mixed-erythroid colonies (E-MIX). Both IL-3 and GM-CSF also induced proliferation of CD34+ in liquid cultures. Proliferative responses to IL-3 were found to be more rapid and stronger than to GM-CSF, although the number of initial responsive cells as judged by autoradiography were comparable. Enhanced proliferation of CD34+ cells both in semi-solid and liquid cultures was obtained in the presence of combinations of IL-3 and GM-CSF. The responses observed were less than additive, with the exception of the development of eosinophil colonies and clusters, where IL-3 and GM-CSF were found to act synergistically. In secondary cultures, proliferative responses to GM-CSF were strongly enhanced by preculture of CD34+ cells in IL-3 for four to 11 days, and to a lesser extent by preculture in GM-CSF. Finally, responses to IL-3 were not affected by preculture of CD34+ cells in the presence of GM-CSF. Our results indicate that there is a wide overlap of cells capable of proliferating either in response to IL-3 or to GM-CSF within the cord blood CD34+ compartment. However, differences in primary proliferation kinetics and increased responsiveness to GM-CSF following preculture suggest the importance of a sequential action of IL-3 and GM-CSF in the expansion of CD34+ cells.
Saeland
S
S
UNICET, Laboratory for Immunological Research, Dardilly, France.
Caux
C
C
Favre
C
C
Duvert
V
V
Pébusque
M J
MJ
Mannoni
P
P
deVries
J E
JE
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D005312:Fetal Blood / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D010641:Phenotype
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D003115:Colony-Stimulating Factors; D004338:Drug Combinations; D006133:Growth Substances; D007377:Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor