Oxidative Responses of Human and Murine Macrophages During Phagocytosis of Leishmania chagasi
| Autor: | Kira R. Gantt, Todd L. Goldman, Eliana T. Nascimento, Bradley E. Britigan, Selma M. B. Jeronimo, Michael L. McCormick, Mary E. Wilson, Melissa A. Miller |
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| Rok vydání: | 2001 |
| Předmět: |
Phagocytosis
Immunology Nitric Oxide Synthase Type II Bone Marrow Cells Biology Nitric Oxide Monocytes Microbiology Cyclic N-Oxides Mice Superoxides parasitic diseases medicine Animals Humans Immunology and Allergy Macrophage RNA Messenger Leishmania infantum Opsonin Cells Cultured Nitrites omega-N-Methylarginine Macrophages Electron Spin Resonance Spectroscopy Leishmaniasis Free Radical Scavengers Leishmania chagasi Oxidants medicine.disease Leishmania biology.organism_classification Oxidative Stress Visceral leishmaniasis Leishmaniasis Visceral Spin Labels Nitric Oxide Synthase Intracellular |
| Zdroj: | The Journal of Immunology. 167:893-901 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection. Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania. However, using electron spin resonance we demonstrated that murine and human macrophages produce O2− during phagocytosis of opsonized promastigotes. Addition of the O2− scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2− enhances macrophage leishmanicidal activity. The importance of NO· produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated. We detected NO· in supernatants from murine, but not human, macrophages infected with L. chagasi. Nonetheless, the iNOS inhibitor NG-monomethyl-l-arginine inhibited IFN-γ-mediated intracellular killing by both murine and human macrophages. According to RNase protection assay and immunohistochemistry, iNOS mRNA and protein were expressed at higher levels in bone marrow of patients with visceral leishmaniasis than in controls. The iNOS protein also increased upon infection of human macrophages with L. chagasi promastigotes in vitro in the presence of IFN-γ. These data suggest that O2− and NO· each contribute to intracellular killing of L. chagasi in human and murine macrophages. |
| Databáze: | OpenAIRE |
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