The cellular basis for enhancement interactions between stem cell factor and the colony stimulating factors.
In cultures of normal mouse fetal liver cells, combination of stem cell factor (SCF) with erythropoietin enhanced erythroid colony formation and, in bone marrow cultures, combination of SCF with interleukin 6 (IL-6) enhanced megakaryocyte colony formation. Combination in marrow cultures of SCF and granulocyte colony stimulating factor (G-CSF) increased cell numbers more than tenfold in developing granulocytic and blast cell colonies. Combination with G-CSF enhanced progenitor cell numbers five-fold in developing blast colonies, but a majority of these were committed macrophage progenitor cells not able to proliferate further with SCF plus G-CSF. Similarly, many of the granulocyte progenitor cells could not proliferate further with this combination of stimuli. This process of amplified but abortive formation of progenitor cells was also noted with use of the combination of SCF plus IL-6 but not with combination of SCF with granulocyte-macrophage CSF (GM-CSF) or Multi-CSF (IL-3). Analysis indicated that where colony size was amplified by combination of a factor with SCF, quantitatively the more important process was amplification of progenitor cell formation rather than amplification of the number of progeny formed by individual committed progenitor cells.
Metcalf
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Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D004921:Erythropoietin / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA / Q000196:embryology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor