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 journalArticle

201 Citations (Scopus)

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

Fingerprint

Leishmania infantum
Phagocytosis
Macrophages
Nitric Oxide Synthase
Visceral Leishmaniasis
Infection
omega-N-Methylarginine
Cutaneous Leishmaniasis
Leishmaniasis
Leishmania
Electron Spin Resonance Spectroscopy
Ribonucleases
Proteins
Bone Marrow
Immunohistochemistry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gantt, K. R., Goldman, T. L., McCormick, M. L., Miller, M. A., Jeronimo, S. M. B., Nascimento, E. T., ... Wilson, M. E. (2001). Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. Journal of Immunology, 167(2), 893-901. https://doi.org/10.4049/jimmunol.167.2.893

Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. / Gantt, K. R.; Goldman, T. L.; McCormick, M. L.; Miller, M. A.; Jeronimo, S. M.B.; Nascimento, E. T.; Britigan, B. E.; Wilson, M. E.

In: Journal of Immunology, Vol. 167, No. 2, 15.07.2001, p. 893-901.

Research output: Contribution to journalArticle

Gantt, KR, Goldman, TL, McCormick, ML, Miller, MA, Jeronimo, SMB, Nascimento, ET, Britigan, BE & Wilson, ME 2001, 'Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi', Journal of Immunology, vol. 167, no. 2, pp. 893-901. https://doi.org/10.4049/jimmunol.167.2.893
Gantt KR, Goldman TL, McCormick ML, Miller MA, Jeronimo SMB, Nascimento ET et al. Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. Journal of Immunology. 2001 Jul 15;167(2):893-901. https://doi.org/10.4049/jimmunol.167.2.893
Gantt, K. R. ; Goldman, T. L. ; McCormick, M. L. ; Miller, M. A. ; Jeronimo, S. M.B. ; Nascimento, E. T. ; Britigan, B. E. ; Wilson, M. E. / Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi. In: Journal of Immunology. 2001 ; Vol. 167, No. 2. pp. 893-901.
@article{2c206591fb494e92a55eea26495fb47e,
title = "Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi",
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.",
author = "Gantt, {K. R.} and Goldman, {T. L.} and McCormick, {M. L.} and Miller, {M. A.} and Jeronimo, {S. M.B.} and Nascimento, {E. T.} and Britigan, {B. E.} and Wilson, {M. E.}",
year = "2001",
month = "7",
day = "15",
doi = "10.4049/jimmunol.167.2.893",
language = "English (US)",
volume = "167",
pages = "893--901",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Oxidative responses of human and murine macrophages during phagocytosis of Leishmania chagasi

AU - Gantt, K. R.

AU - Goldman, T. L.

AU - McCormick, M. L.

AU - Miller, M. A.

AU - Jeronimo, S. M.B.

AU - Nascimento, E. T.

AU - Britigan, B. E.

AU - Wilson, M. E.

PY - 2001/7/15

Y1 - 2001/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035879106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035879106&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.167.2.893

DO - 10.4049/jimmunol.167.2.893

M3 - Article

C2 - 11441096

AN - SCOPUS:0035879106

VL - 167

SP - 893

EP - 901

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -