Differential Effects of Granulocyte/Macrophage Colony-Stimulating Factor (GM-CSF) in Enhancing Macrophage Resistance toLegionella pneumophilavsCandida albicans

It has been reported that granulocyte/macrophage colony-stimulating factor (GM-CSF), one of the hemopoietic growth factors which regulates the function of phagocytic cells, is a potent activator of cultured macrophages and induces antimicrobial activities as well as differentiation of precursor cells. In this study, we examined the ability of recombinant murine GM-CSF to activate mouse peritoneal macrophages to restrict the growth of two different microorganisms,Candida albicansandLegionella pneumophila,both of which are important opportunistic pathogens in an immunocompromised host. Treatment of thioglycollate-elicited BDF1 mouse macrophages with GM-CSF for 24 hr enhanced the anti-C. albicansactivity of the macrophages in terms of inhibiting growth of the fungi. Reactive oxygen (H2O2) and IL-1 production by the macrophages were also enhanced by treatment with GM-CSF. However, no enhancement of anti-L. pneumophilaactivity of macrophages obtained from either susceptible A/J or resistant BDF1 mice toL. pneumophilainfection after treatment with up to 1000 units/ml GM-CSF was observed under the same conditions. When the treatment time was extended to 72 hr, GM-CSF was still unable to induce anti-L. pneumophilaactivity. As a control study, treatment with recombinant IFN-γ enhanced both anti-Candidaand anti-Legionellaactivity in cultured macrophages under the same conditions used in the GM-CSF study. Measurement of cellular iron content revealed the low iron content in IFN-γ-treated macrophages, but no decrease of iron in GM-CSF-treated macrophages compared with the control group, indicating a possible involvement of iron as a key factor in anti-L. pneumophilaactivity. Thus, the results of the study show that GM-CSF activation of elicited peritoneal macrophages is selective with regard to the type of antimicrobial activity induced.