The role of hemopoietic growth factors in self-renewal and differentiation of IL-3-dependent multipotential stem cells.
A multipotent hemopoietic cell line has been employed to assess the influence of the hemopoietic growth factors, IL-3, GM-CSF, G-CSF, and CSF-1 on the processes of self-renewal, the generation of lineage restricted progenitor cells and the production of mature neutrophils and macrophages. At a high concentration of IL-3, the cells undergo self-renewal and demonstrate little or no ability to undergo differentiation in the presence of the other growth factors. In the absence of IL-3, the cells show minimal (GM-CSF) or no (G-CSF or CSF-1) ability to respond to these other growth factors. When combined with a low concentration of IL-3, the ability of the cells to respond to GM-CSF, G-CSF, and CSF-1 is enhanced and a selective preference for the neutrophil or macrophage lineage is seen depending on the combination used, i.e., the presence of CSF-1 preferentially promotes macrophage development and G-CSF preferentially promotes neutrophil development. Conditions optimal for neutrophil development were seen using a combination of low IL-3 concentrations plus GM-CSF plus G-CSF. In such conditions, the cells undergo extensive proliferation and progressively lose their clonogenic potential (i.e., differentiation much greater than self-renewal) and acquire the biochemical markers characteristic of fully mature phagocytes.
Experimental Haematology Department, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Withington, Manchester, United Kingdom.
C M
CM
Heyworth
T M
TM
Dexter
O
O
Kan
A D
AD
Whetton
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004347:Drug Interactions; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007377:Interleukin-3 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor