The synergistic influence of human interferon-γ and interferon-α on suppression of hematopoietic progenitor cells is additive with the enhanced sensitivity of these cells to inhibition by interferons at low oxygen tension in vitro

Hal Broxmeyer, S. Cooper, B. Y. Rubin, M. W. Taylor

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Abstract

The influences of human interferons - natural γ (2 x 107 NIH reference U/mg), recombinant γ (~5 x 106 U/mg), natural α (1.4 x 108 international reference U/mg), and natural β (106 international reference U/mg) - were evaluated alone or in combination for their effects in vitro on colony formation by low density human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in normal incubator (~20%) O2 tension or low (5%) O2 tension. Alone, these interferons demonstrated the same dose response inhibitory curves, as we reported previously, when cells were grown at 20% O2. Recombinant IFN-γ gave the same dose response curve as natural IFN-γ. Natural or recombinant interferon synergized with IFN-α to suppress colony formation at concentrations that were approximately 2 log units lower than that required by either interferon alone. Equal concentrations of these interferons were not needed for the synergistic effect and were still apparent when one was present at concentrations of 2 log units less than the other. IFN-γ synergized to a lesser extent with IFN-β, but IFN-α did not synergize with IFN-β. Cells grown at 5% O2 were more sensitive to inhibition by 2 log units less IFN-γ or IFN-α, and this effect was additive with the synergistic effects of IFN-γ and IFN-α together. These results may have physiological, pathological, and/or clinical relevance.

Original languageEnglish
Pages (from-to)2502-2506
Number of pages5
JournalJournal of Immunology
Volume135
Issue number4
StatePublished - 1985

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Hematopoietic Stem Cells
Interferons
Oxygen
Myeloid Progenitor Cells
Incubators
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Granulocytes
Stem Cells
Bone Marrow
Macrophages
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "The synergistic influence of human interferon-γ and interferon-α on suppression of hematopoietic progenitor cells is additive with the enhanced sensitivity of these cells to inhibition by interferons at low oxygen tension in vitro",
abstract = "The influences of human interferons - natural γ (2 x 107 NIH reference U/mg), recombinant γ (~5 x 106 U/mg), natural α (1.4 x 108 international reference U/mg), and natural β (106 international reference U/mg) - were evaluated alone or in combination for their effects in vitro on colony formation by low density human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5{\%} CO2 in normal incubator (~20{\%}) O2 tension or low (5{\%}) O2 tension. Alone, these interferons demonstrated the same dose response inhibitory curves, as we reported previously, when cells were grown at 20{\%} O2. Recombinant IFN-γ gave the same dose response curve as natural IFN-γ. Natural or recombinant interferon synergized with IFN-α to suppress colony formation at concentrations that were approximately 2 log units lower than that required by either interferon alone. Equal concentrations of these interferons were not needed for the synergistic effect and were still apparent when one was present at concentrations of 2 log units less than the other. IFN-γ synergized to a lesser extent with IFN-β, but IFN-α did not synergize with IFN-β. Cells grown at 5{\%} O2 were more sensitive to inhibition by 2 log units less IFN-γ or IFN-α, and this effect was additive with the synergistic effects of IFN-γ and IFN-α together. These results may have physiological, pathological, and/or clinical relevance.",
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T1 - The synergistic influence of human interferon-γ and interferon-α on suppression of hematopoietic progenitor cells is additive with the enhanced sensitivity of these cells to inhibition by interferons at low oxygen tension in vitro

AU - Broxmeyer, Hal

AU - Cooper, S.

AU - Rubin, B. Y.

AU - Taylor, M. W.

PY - 1985

Y1 - 1985

N2 - The influences of human interferons - natural γ (2 x 107 NIH reference U/mg), recombinant γ (~5 x 106 U/mg), natural α (1.4 x 108 international reference U/mg), and natural β (106 international reference U/mg) - were evaluated alone or in combination for their effects in vitro on colony formation by low density human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in normal incubator (~20%) O2 tension or low (5%) O2 tension. Alone, these interferons demonstrated the same dose response inhibitory curves, as we reported previously, when cells were grown at 20% O2. Recombinant IFN-γ gave the same dose response curve as natural IFN-γ. Natural or recombinant interferon synergized with IFN-α to suppress colony formation at concentrations that were approximately 2 log units lower than that required by either interferon alone. Equal concentrations of these interferons were not needed for the synergistic effect and were still apparent when one was present at concentrations of 2 log units less than the other. IFN-γ synergized to a lesser extent with IFN-β, but IFN-α did not synergize with IFN-β. Cells grown at 5% O2 were more sensitive to inhibition by 2 log units less IFN-γ or IFN-α, and this effect was additive with the synergistic effects of IFN-γ and IFN-α together. These results may have physiological, pathological, and/or clinical relevance.

AB - The influences of human interferons - natural γ (2 x 107 NIH reference U/mg), recombinant γ (~5 x 106 U/mg), natural α (1.4 x 108 international reference U/mg), and natural β (106 international reference U/mg) - were evaluated alone or in combination for their effects in vitro on colony formation by low density human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in normal incubator (~20%) O2 tension or low (5%) O2 tension. Alone, these interferons demonstrated the same dose response inhibitory curves, as we reported previously, when cells were grown at 20% O2. Recombinant IFN-γ gave the same dose response curve as natural IFN-γ. Natural or recombinant interferon synergized with IFN-α to suppress colony formation at concentrations that were approximately 2 log units lower than that required by either interferon alone. Equal concentrations of these interferons were not needed for the synergistic effect and were still apparent when one was present at concentrations of 2 log units less than the other. IFN-γ synergized to a lesser extent with IFN-β, but IFN-α did not synergize with IFN-β. Cells grown at 5% O2 were more sensitive to inhibition by 2 log units less IFN-γ or IFN-α, and this effect was additive with the synergistic effects of IFN-γ and IFN-α together. These results may have physiological, pathological, and/or clinical relevance.

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