Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha: Synergism with recombinant human interferon-gamma

L. Lu, D. Walker, C. D. Graham, A. Waheed, R. K. Shadduck, Hal Broxmeyer

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Abstract

The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-α) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-γ) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-α or rhuIFN-γ enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)-CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two-color fluorescence using a dye laster flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While 'constitutive' release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-α or rhuIFN-γ was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-α and rhuIFN-γ synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-α and IFN-γ in the release of CSFs from cells of the mononuclear phagocytic lineage.

Original languageEnglish
Pages (from-to)34-41
Number of pages8
JournalBlood
Volume72
Issue number1
StatePublished - 1988

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Colony-Stimulating Factors
Macrophage Colony-Stimulating Factor
Histocompatibility Antigens Class II
Monocytes
Tumor Necrosis Factor-alpha
HLA-DR Antigens
Myeloid Progenitor Cells
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Conditioned Culture Medium
Phycoerythrin
human IFNG protein
human TNF protein
Molecules
Granulocyte Colony-Stimulating Factor
Phagocytes
Flow cytometry
Macrophages
Fluorescein
Granulocytes

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha: Synergism with recombinant human interferon-gamma",
abstract = "The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-α) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-γ) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-α or rhuIFN-γ enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)-CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two-color fluorescence using a dye laster flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While 'constitutive' release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-α or rhuIFN-γ was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-α and rhuIFN-γ synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-α and IFN-γ in the release of CSFs from cells of the mononuclear phagocytic lineage.",
author = "L. Lu and D. Walker and Graham, {C. D.} and A. Waheed and Shadduck, {R. K.} and Hal Broxmeyer",
year = "1988",
language = "English",
volume = "72",
pages = "34--41",
journal = "Blood",
issn = "0006-4971",
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T1 - Enhancement of release from MHC class II antigen-positive monocytes of hematopoietic colony stimulating factors CSF-1 and G-CSF by recombinant human tumor necrosis factor-alpha

T2 - Synergism with recombinant human interferon-gamma

AU - Lu, L.

AU - Walker, D.

AU - Graham, C. D.

AU - Waheed, A.

AU - Shadduck, R. K.

AU - Broxmeyer, Hal

PY - 1988

Y1 - 1988

N2 - The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-α) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-γ) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-α or rhuIFN-γ enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)-CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two-color fluorescence using a dye laster flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While 'constitutive' release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-α or rhuIFN-γ was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-α and rhuIFN-γ synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-α and IFN-γ in the release of CSFs from cells of the mononuclear phagocytic lineage.

AB - The influence of purified recombinant human tumor necrosis factor-alpha (rhuTNF-α) was assessed alone and in combination with purified recombinant human interferon gamma (rhuIFN-γ) for its effects on enhancing release from human monocytes of activities that stimulate colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells. RhuTNF-α or rhuIFN-γ enhanced release of colony stimulating factors (CSFs), which were determined by a combination of human and mouse colony assays, morphological assessment of colony types and neutralization studies with anti-human macrophage CSF (CSF-1) and anti-human granulocyte (G)-CSF to be CSF-1 and G-CSF. The activity in the uninduced and induced monocyte conditioned media (CM) for CFU-GM-type colonies and clusters was attributed to the presence of both CSF-1 and G-CSF, while the activity in the monocyte CM for BFU-E and CFU-GEMM colonies was attributed to the presence of G-CSF. Monocytes were separated by two-color fluorescence using a dye laster flow cytometry system with cells labeled with anti-leu M3 conjugated with fluorescein isothiocyanate and anti-HLA-DR conjugated with phycoerythrin. While 'constitutive' release of CSFs from monocytes was apparent from both the leu M3+, HLA-DR+ and the leu M3+, HLA-DR- (low density or negative DR) fractions, enhanced release of CSFs in response to rhuTNF-α or rhuIFN-γ was confined to the leu M3+, HLA-DR+ population of cells. RhuTNF-α and rhuIFN-γ synergized to enhance release of CSFs such that low concentrations of each molecule, which were inactive when used alone, were active when the two molecules were used together. These studies suggest a role, at least in vitro, for TNF-α and IFN-γ in the release of CSFs from cells of the mononuclear phagocytic lineage.

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