Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in combination with macrophage colony-stimulating factor (CSF-1) can stimulate colony-forming cells in bone marrow (BM) that have a high proliferative capacity. In cultures of BM from mice treated with 5-fluorouracil (FU) eight days before sampling, GM-CSF alone or in combination with CSF-1 stimulated the formation of large macrophage colonies with diameters greater than 0.5 mm. CSF-1 alone, at 800 units or greater, also stimulated larger colonies; however, these colonies were always less than 1.1 mm in diameter, whereas GM-CSF in combination with CSF-1 stimulated many colonies with diameters between 1 and 4 mm. At all doses of CSF-1 tested, the combination of factors resulted in a synergistic increase in colonies with diameters greater than 1.0 or 2.0 mm. Analysis of the incidence of colony-forming cells in the BM of normal mice and mice 2, 4, 6, and 8 days after FU treatment demonstrated that the progenitor cells stimulated by GM-CSF alone or in combination with CSF-1 were depleted by FU treatment in vivo and regenerated more rapidly than did the macrophage progenitors (M-CFC) stimulated by CSF-1 alone. This is similar to the properties of the previously described high-proliferative potential, colony-forming cell (HPP-CFC) that is responsive to interleukin-3 plus CSF-1 but not the HPP-CFC stimulated by hematopoietin 1 plus CSF-1. These data suggest that GM-CSF plus CSF-1 act synergistically to stimulate a population of progenitor cells that have a high proliferative potential and have properties similar to those of the population of HPP-CFC stimulated by interleukin-3 plus CSF-1.
McNiece
I K
IK
University of Virginia, School of Medicine, Charlottesville 22908.
Robinson
B E
BE
Quesenberry
P J
PJ
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005472:Fluorouracil