Synergistic actions of stem cell factor and other burst-promoting activities on proliferation of CD34+ highly purified blood progenitors expressing HLA-DR or different levels of c-kit protein.
We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GM-CSF, and IL-9 showed significant BPA when CD34+HLA-DR+ cells were used as the target population. IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3. SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs did not show synergistic actions supporting erythroid-burst formation. However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34+c-kithigh cells were used as the target, SCF showed a much stronger BPA. Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34+c-kitlow cells were used as the target, SCF, IL-3, and GM-CSF could express BPA. In contrast, IL-9 alone failed to support erythroid-burst formation. Because CD34+c-kithigh cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34+c-kitlow cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development.
Sonoda
Y
Y
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Sakabe
H
H
Ohmisono
Y
Y
Tanimukai
S
S
Yokota
S
S
Nakagawa
S
S
Clark
S C
SC
Abe
T
T
D000818:Animals; D015703:Antigens, CD; D018952:Antigens, CD34; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D004926:Escherichia coli; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D013736:Testicular Neoplasms / Q000097:blood / Q000628:therapy
D015703:Antigens, CD; D018952:Antigens, CD34; D006684:HLA-DR Antigens; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D016906:Interleukin-9; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases