Killing of Histoplasma capsulatum by macrophage colony stimulating factor-treated human monocyte-derived macrophages: role for reactive oxygen intermediates.
The interaction of human macrophages with the yeast-form of Histoplasma capsulatum was studied. The use of culture and a short-term assay period instead of microscopy gave direct evidence of the fungicidal activity of human macrophages. The present study reports the novel finding of fungicidal activity of macrophages derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). The induction of fungicidal activity by this cytokine was dose dependent. MCSF at 10,000 U/ml was optimal with 73(SD3)% killing. Inhibition of macrophage killing by superoxide dismutase (SOD), but not catalase (CAT) or N-monomethyl-L-arginine (NMMA), established the role of the superoxide anion in the killing mechanism. The fungistatic activity of MCSF-derived human macrophages in a 24-h assay was also dose dependent and was not inhibited by SOD, CAT or NMMA. MCSF at 10,000 U/ml produced optimal macrophage fungistatic activity, 34.6(SD4)%.
Desai
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G
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA.
Nassar
F
F
Brummer
E
E
Stevens
D A
DA
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D016166:Free Radical Scavengers; D006658:Histoplasma / Q000276:immunology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase