Gamma interferon induces monocyte killing of Listeria monocytogenes by an oxygen-dependent pathway; alpha- or beta-interferons by oxygen-independent pathways.
Human peripheral blood monocytes purified by counterflow centrifugal elutriation were treated with recombinant interferons-gamma (IFN-gamma), alpha (IFN-alpha), or beta (IFN-beta)--and tested for their capacity to kill Listeria monocytogenes. All three IFNs increased the monocyte bactericidal activity in a dose-dependent fashion. Exogeneous catalase, an inhibitor of monocyte-generated hydrogen peroxide, did not affect bactericidal activity. However, exogenous superoxide dismutase inhibited killing by IFN-gamma-activated monocytes, but not by IFN-alpha- or IFN-beta-activated monocytes. By contrast, exogenous soybean trypsin inhibitor inhibited killing by IFN-alpha or IFN-beta-activated monocytes, but not by IFN-gamma-activated monocytes. Combinations of IFN-gamma and IFN-alpha resulted in no increase in bactericidal activity. Finally, treatment with IFN-gamma resulted in different receptiveness of the cell to subsequent oxidative burst-stimulating signals than did treatment with either IFN-alpha or IFN-beta. These results suggest that monocytes treated with IFN-gamma kill L. monocytogenes by an oxygen-dependent mechanism, but treatment with IFN-alpha or IFN-beta elicits principally oxygen-independent mechanisms.
Peck
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Central Research Unit, F. Hoffmann-La Roche & Co., Ltd., Basel, Switzerland.
D001770:Blood Bactericidal Activity / Q000187:drug effects*; D005609:Free Radicals; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010100:Oxygen / Q000378:metabolism*; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000494:pharmacology
D005609:Free Radicals; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D013482:Superoxide Dismutase; D010100:Oxygen