Mast cell growth factor (c-kit ligand) enhances cytokine stimulation of proliferation of the human factor-dependent cell line, M07e

P. C. Hendrie, K. Miyazawa, Y. C. Yang, C. D. Langefeld, Hal Broxmeyer

Research output: Contribution to journalArticle

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Abstract

Murine mast cell growth factor (muMGF), a c-kit ligand, has additive to greater-than-additive effects on in vitro colony formation of murine and human myeloid progenitor cells stimulated with erythropoietin, granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin (IL)-3. To confirm direct-acting effects on responding cells, MGF was assessed alone and in combination with other cytokines for effects on the proliferation of the human factor-dependent cell line, M07e. Proliferation was assayed in liquid culture by [3H]thymidine uptake and in semisolid medium by colony formation. Purified recombinant (r) muMGF (25-50 ng/ml) by itself had proliferative activity but less than r human (hu) GM-CSF. In combination with rhuGM-CSF (250 U/ml) or IL-3 (500 U/ml), rmuMGF (25 ng/ml) enhanced [3H]thymidine uptake two- to sevenfold greater than the sum of the effects of each factor alone, Similar enhancement was seen in the number and size of colonies formed. When MGF was used in combination with rhuIL-4 (500-1000 U/ml), rhuIL-6 (5 ng/ml), rhuIL-9 (5-10 U/ml), or rhu interferon gamma (IFN-γ; 250-500 U/ml) (factors that alone stimulate little proliferation), [3H]thymidine uptake and colony formation were respectively increased 2- to 11- and 3- to 55-fold over the sum of each of the effects of the factors alone. Exposure of 5 x 105 cells/ml to 50 ng/ml MGF for 24 h, a time during which synergism is noted with MGF plus either GM-CSF or IL-3, did not change GM-CSF or IL-3 receptor binding affinity or the number of binding sites. Exposure of cells to MGF for 48 h did not alter subsequent GM-CSF- or IL-3-stimulated proliferation. The results suggest that M07e cells will be useful as a model for the analysis of intracellular biochemical mechanisms of the direct-acting proliferative and synergistic effects of MGF.

Original languageEnglish
Pages (from-to)1031-1037
Number of pages7
JournalExperimental Hematology
Volume19
Issue number10
StatePublished - 1991

Fingerprint

Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-3
Cytokines
Cell Line
Thymidine
Interleukin-3 Receptors
Myeloid Progenitor Cells
Erythropoietin
Interferon-gamma
Binding Sites

Keywords

  • GM-CSF
  • IFN-γ
  • IL-3
  • IL-4
  • IL-6
  • IL-9
  • M07e cells
  • MGF

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Mast cell growth factor (c-kit ligand) enhances cytokine stimulation of proliferation of the human factor-dependent cell line, M07e. / Hendrie, P. C.; Miyazawa, K.; Yang, Y. C.; Langefeld, C. D.; Broxmeyer, Hal.

In: Experimental Hematology, Vol. 19, No. 10, 1991, p. 1031-1037.

Research output: Contribution to journalArticle

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AU - Langefeld, C. D.

AU - Broxmeyer, Hal

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