Induction of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in bone marrow and fractionated marrow cell populations by interleukin 3 (IL-3): IL-3-mediated positive feedback mechanisms of granulopoiesis

Growth Factors. 1994;11(1):71-9. doi: 10.3109/08977199409015052.


Interleukin 3 (IL-3) induces proliferation and differentiation of mast cell progenitors in vitro, whereas it induces granulocytosis in vivo. In this paper, a positive feedback mechanism of granulopoiesis was studied in order to elucidate the granulocytosis induced by IL-3 in mouse. IL-3 induced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in total bone marrow cells and a marrow adherent cell population. In fractionated marrow cell populations, a different expression pattern of induction of IL-3 stimulation was observed; GM-CSF was expressed in macrophages and fraction 1 (P < 1.061) and 2(1.061 < P 1.074) of bone marrow cells fractionated by equilibrium density centrifugation, G-CSF was expressed in macrophages and fraction 2 and 3 (1.074 < P < 1.097), and interleukin 6 (IL-6) in macrophages and fraction 1 to 3. These results indicate a hierarchical regulation of cytokine production and the existence of a positive feedback mechanism in granulopoiesis. IL-6, induced by IL-3, stimulates stem cells into cycle and induces stem cells to respond to IL-3. The stem cells differentiate to granulocyte-macrophage colony-forming cells by the combined effect of IL-3 and IL-6. IL-3 also induces GM- and G-CSF expression which in turn makes granulocyte-macrophage colony-forming cells differentiate to granulocytes. These factors organize a cytokine network in granulopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Marrow / drug effects*
  • Bone Marrow / metabolism
  • Bone Marrow Cells
  • Cell Line
  • Cells, Cultured
  • DNA Primers / genetics
  • Feedback
  • Gene Expression Regulation / drug effects
  • Granulocyte Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocytes / cytology
  • Granulocytes / drug effects
  • Granulocytes / metabolism
  • Hematopoiesis / drug effects
  • In Vitro Techniques
  • Interleukin-3 / genetics
  • Interleukin-3 / pharmacology*
  • Interleukin-6 / genetics
  • Mice
  • Mice, Inbred C3H
  • Models, Biological
  • Molecular Sequence Data
  • Polymerase Chain Reaction


  • DNA Primers
  • Interleukin-3
  • Interleukin-6
  • Granulocyte Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor