Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi

K. R. Gantt, T. L. Goldman, M. L. McCormick, M. A. Miller, S. M.B. Jeronimo, E. T. Nascimento, B. E. Britigan, M. E. Wilson

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalJournal of Immunology
Volume167
Issue number2
DOIs
StatePublished - Jul 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi'. Together they form a unique fingerprint.

Cite this