Colony stimulating factor-1 is a negative regulator of the macrophage respiratory burst.
Several cytokines have previously been shown to prime macrophages for enhanced release of oxygen radicals in response to subsequent stimulation. We now demonstrate that the presence of the macrophage-specific colony stimulating factor-1 (CSF-1) inhibits the priming of murine macrophages by a variety of agents including tumor necrosis factor alpha, granulocyte/macrophage colony stimulating factor, interferon-gamma, and bacterial lipopolysaccharide. CSF-1 is also able to reduce the respiratory burst in the absence of priming. Our results indicate that CSF-1 is a potent negative regulator of the macrophage respiratory burst which acts to oppose the priming (enhancing) action of macrophage activating agents. We propose that CSF-1 may have a potentially important and previously unrecognized, role as a physiological regulator which restricts or terminates the activation of macrophages in order to prevent an uncontrolled inflammatory reaction.
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
W A
WA
Phillips
J A
JA
Hamilton
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004926:Escherichia coli; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D010101:Oxygen Consumption / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor