Synergistic inhibition of human marrow granulocyte-macrophage progenitor cells by prostaglandin E and recombinant interferon-alpha, -beta, and -gamma and an effect mediated by tumor necrosis factor.
The effects of prostaglandin E (PGE) and recombinant human interferon-alpha, -beta, and -gamma alone and in combination were tested for their effects on the proliferation of human bone marrow granulocyte-macrophage colony-forming units (GM-CFU). When tested alone, both classes of cytokines inhibited GM-CFU proliferation. In combination, PGE and all three types of recombinant interferons synergized in their ability to inhibit GM-CFU proliferation. Progressive enrichment for marrow GM-CFU indicated that the synergistic effects of PGE and interferon were dependent upon the presence of marrow-adherent cells. Studies using conditioned media from marrow-adherent cells prepared in the presence of interferon-alpha, -beta, and -gamma indicated that adherent cells produced a soluble factor in the presence of interferons that subsequently synergized with PGE in inhibiting GM-CFU proliferation. Neutralization of this conditioned media with a monoclonal antibody to tumor necrosis factor abrogated the synergistic inhibition of GM-CFU observed in the presence of PGE. The addition of recombinant tumor necrosis factor and PGE to accessory cell-depleted bone marrow resulted in synergystic inhibition of GM-CFU proliferation.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D015232:Dinoprostone; D004357:Drug Synergism; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015232:Dinoprostone