Suppressive biological activity of a synthetic pentapeptide on highly enriched human and murine marrow hematopoietic progenitors: Synergism with recombinant human tumor necrosis factor-alpha and interferon-gamma

L. Lu, P. Foa, F. Chillemi, R. N. Shen, Z. H. Lin, C. Carow, Hal Broxmeyer

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Abstract

The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys (SP1) was evaluated in vitro alone and in combination with recombinant human tumor necrosis factor-alpha TNF-α) and/or interferon-gamma (IFN-γ) for effects on colony formation by hematopoietic progenitor cells (HPC) present in low-density (LD), nonadherent low-density T-lymphocyte-depleted (NALT-), and high enriched sorted progenitor cells from normal human bone marrow. Progenitor cells in NALT- fractions were further enriched by cell sorting two-color fluorescence on a Coulter Epics 753 flow cytometry apparatus with My10 and HLA-DR monoclonal antibodies. The sorted My10+++DR+ progenitor cell population had a cloning efficiency of up to 38% for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and multipotential colony-forming units (CFU-GEMM). SP1 inhibited, by up to 86%, each of the colony-forming cells in a dose-dependent fashion. The sensitivities of the different progenitor cells to inhibition by the pentapeptide were the same when My10+++DR+ marrow cells were used, and the progenitor cells in the My10+++DR+ fraction were more sensitive than the cells in the LD or NALT- fraction to inhibition by SP1. The suppressive activity of SP1 on purified HPC was confirmed when 10-3 M SP1 completely inhibited colony and cluster formation from a population of mouse bone marrow cells in which one of two cells was a CFU-GM. The effects of SP1 were not absolutely cell-cycle-specific for human HPC, but the non-S-phase cells were less sensitive than the S-phase cells to the suppressive effects of SP1. SP1 synergized with TNF-α and/or IFN-γ to inhibit proliferation of progenitor cells using both LD or My10+++DR+ human marrow cells stimulated by recombinant human interleukin 3 (IL-3). These studies suggest that the suppressive effect of SP1 occurs in the absence of certain accessory cells (e.g., monocytes and T-lymphocytes), that this effect may be mediated directly at the level of the HPC, and that this pentapeptide can be considered a candidate modulatory molecule for HPC proliferation.

Original languageEnglish
Pages (from-to)935-941
Number of pages7
JournalExperimental Hematology
Volume17
Issue number9
StatePublished - 1989

Fingerprint

Interferon-alpha
Interferon-gamma
Tumor Necrosis Factor-alpha
Bone Marrow
Stem Cells
Hematopoietic Stem Cells
Granulocyte-Macrophage Progenitor Cells
T-Lymphocytes
Erythroid Precursor Cells
Myeloid Progenitor Cells
human TNF protein
Interleukin-3
HLA-DR Antigens
S Phase
Bone Marrow Cells
Population
Organism Cloning
Monocytes
Cell Cycle
Flow Cytometry

ASJC Scopus subject areas

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

Cite this

@article{15e79a44d33f4cbf993a3ad523dbf545,
title = "Suppressive biological activity of a synthetic pentapeptide on highly enriched human and murine marrow hematopoietic progenitors: Synergism with recombinant human tumor necrosis factor-alpha and interferon-gamma",
abstract = "The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys (SP1) was evaluated in vitro alone and in combination with recombinant human tumor necrosis factor-alpha TNF-α) and/or interferon-gamma (IFN-γ) for effects on colony formation by hematopoietic progenitor cells (HPC) present in low-density (LD), nonadherent low-density T-lymphocyte-depleted (NALT-), and high enriched sorted progenitor cells from normal human bone marrow. Progenitor cells in NALT- fractions were further enriched by cell sorting two-color fluorescence on a Coulter Epics 753 flow cytometry apparatus with My10 and HLA-DR monoclonal antibodies. The sorted My10+++DR+ progenitor cell population had a cloning efficiency of up to 38{\%} for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and multipotential colony-forming units (CFU-GEMM). SP1 inhibited, by up to 86{\%}, each of the colony-forming cells in a dose-dependent fashion. The sensitivities of the different progenitor cells to inhibition by the pentapeptide were the same when My10+++DR+ marrow cells were used, and the progenitor cells in the My10+++DR+ fraction were more sensitive than the cells in the LD or NALT- fraction to inhibition by SP1. The suppressive activity of SP1 on purified HPC was confirmed when 10-3 M SP1 completely inhibited colony and cluster formation from a population of mouse bone marrow cells in which one of two cells was a CFU-GM. The effects of SP1 were not absolutely cell-cycle-specific for human HPC, but the non-S-phase cells were less sensitive than the S-phase cells to the suppressive effects of SP1. SP1 synergized with TNF-α and/or IFN-γ to inhibit proliferation of progenitor cells using both LD or My10+++DR+ human marrow cells stimulated by recombinant human interleukin 3 (IL-3). These studies suggest that the suppressive effect of SP1 occurs in the absence of certain accessory cells (e.g., monocytes and T-lymphocytes), that this effect may be mediated directly at the level of the HPC, and that this pentapeptide can be considered a candidate modulatory molecule for HPC proliferation.",
author = "L. Lu and P. Foa and F. Chillemi and Shen, {R. N.} and Lin, {Z. H.} and C. Carow and Hal Broxmeyer",
year = "1989",
language = "English",
volume = "17",
pages = "935--941",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "9",

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TY - JOUR

T1 - Suppressive biological activity of a synthetic pentapeptide on highly enriched human and murine marrow hematopoietic progenitors

T2 - Synergism with recombinant human tumor necrosis factor-alpha and interferon-gamma

AU - Lu, L.

AU - Foa, P.

AU - Chillemi, F.

AU - Shen, R. N.

AU - Lin, Z. H.

AU - Carow, C.

AU - Broxmeyer, Hal

PY - 1989

Y1 - 1989

N2 - The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys (SP1) was evaluated in vitro alone and in combination with recombinant human tumor necrosis factor-alpha TNF-α) and/or interferon-gamma (IFN-γ) for effects on colony formation by hematopoietic progenitor cells (HPC) present in low-density (LD), nonadherent low-density T-lymphocyte-depleted (NALT-), and high enriched sorted progenitor cells from normal human bone marrow. Progenitor cells in NALT- fractions were further enriched by cell sorting two-color fluorescence on a Coulter Epics 753 flow cytometry apparatus with My10 and HLA-DR monoclonal antibodies. The sorted My10+++DR+ progenitor cell population had a cloning efficiency of up to 38% for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and multipotential colony-forming units (CFU-GEMM). SP1 inhibited, by up to 86%, each of the colony-forming cells in a dose-dependent fashion. The sensitivities of the different progenitor cells to inhibition by the pentapeptide were the same when My10+++DR+ marrow cells were used, and the progenitor cells in the My10+++DR+ fraction were more sensitive than the cells in the LD or NALT- fraction to inhibition by SP1. The suppressive activity of SP1 on purified HPC was confirmed when 10-3 M SP1 completely inhibited colony and cluster formation from a population of mouse bone marrow cells in which one of two cells was a CFU-GM. The effects of SP1 were not absolutely cell-cycle-specific for human HPC, but the non-S-phase cells were less sensitive than the S-phase cells to the suppressive effects of SP1. SP1 synergized with TNF-α and/or IFN-γ to inhibit proliferation of progenitor cells using both LD or My10+++DR+ human marrow cells stimulated by recombinant human interleukin 3 (IL-3). These studies suggest that the suppressive effect of SP1 occurs in the absence of certain accessory cells (e.g., monocytes and T-lymphocytes), that this effect may be mediated directly at the level of the HPC, and that this pentapeptide can be considered a candidate modulatory molecule for HPC proliferation.

AB - The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys (SP1) was evaluated in vitro alone and in combination with recombinant human tumor necrosis factor-alpha TNF-α) and/or interferon-gamma (IFN-γ) for effects on colony formation by hematopoietic progenitor cells (HPC) present in low-density (LD), nonadherent low-density T-lymphocyte-depleted (NALT-), and high enriched sorted progenitor cells from normal human bone marrow. Progenitor cells in NALT- fractions were further enriched by cell sorting two-color fluorescence on a Coulter Epics 753 flow cytometry apparatus with My10 and HLA-DR monoclonal antibodies. The sorted My10+++DR+ progenitor cell population had a cloning efficiency of up to 38% for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and multipotential colony-forming units (CFU-GEMM). SP1 inhibited, by up to 86%, each of the colony-forming cells in a dose-dependent fashion. The sensitivities of the different progenitor cells to inhibition by the pentapeptide were the same when My10+++DR+ marrow cells were used, and the progenitor cells in the My10+++DR+ fraction were more sensitive than the cells in the LD or NALT- fraction to inhibition by SP1. The suppressive activity of SP1 on purified HPC was confirmed when 10-3 M SP1 completely inhibited colony and cluster formation from a population of mouse bone marrow cells in which one of two cells was a CFU-GM. The effects of SP1 were not absolutely cell-cycle-specific for human HPC, but the non-S-phase cells were less sensitive than the S-phase cells to the suppressive effects of SP1. SP1 synergized with TNF-α and/or IFN-γ to inhibit proliferation of progenitor cells using both LD or My10+++DR+ human marrow cells stimulated by recombinant human interleukin 3 (IL-3). These studies suggest that the suppressive effect of SP1 occurs in the absence of certain accessory cells (e.g., monocytes and T-lymphocytes), that this effect may be mediated directly at the level of the HPC, and that this pentapeptide can be considered a candidate modulatory molecule for HPC proliferation.

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