Effect of interleukin-4 on the growth of granulocyte-macrophage progenitor cells stimulated by hematopoietic growth factors.
The effects of recombinant murine interleukin-4 (rmIL-4) on murine granulocyte-macrophage progenitor cells (CFU-GM) were investigated in the presence or absence of recombinant human granulocyte colony stimulating factor (rhG-CSF), recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF) or recombinant murine interleukin-3 (rmIL-3) both in serum-free and serum-containing cultures. IL-4 alone could not support any CFU-GM colony formation in both culture systems. In serum-free cultures, IL-4 inhibited CFU-GM colony formation stimulated by G-CSF, GM-CSF or IL-3 from whole bone marrow cells (whole BM cells), nonadherent, nonphagocytic and T cell-depleted BM cells (fractionated BM cells) or whole BM cells of 5-Fluorouracil (5-FU) treated mice. On the other hand, in serum-containing cultures, IL-4 inhibited CFU-GM colony formation stimulated by GM-CSF or IL-3, but IL-4 dose-dependently enhanced G-CSF-stimulated colony formation from both whole and fractionated BM cells. Morphological examinations revealed that IL-4 predominantly inhibited granulocyte-lineage colony formation stimulated by GM-CSF or IL-3 in both culture systems. When combined with G-CSF, IL-4 predominantly inhibited granulocyte-lineage colony formation and relatively increased macrophage-lineage colonies, but in serum-containing culture, IL-4 significantly increased macrophage-lineage colony formation. The results of the present study suggest that IL-4 has an inhibitory effect on the factors (G-CSF, GM-CSF, IL-3)-dependent CFU-GM colony formation in serum-free condition and enhances only G-CSF-stimulated CFU-GM colony formation in serum-containing condition.
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
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Sato
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Misago
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Tsukada
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Kikuchi
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Oda
S
S
Chiba
S
S
Eto
D000818:Animals; D002455:Cell Division; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000166:cytology*; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor