Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide

Rami M Mukbel; Calvin Patten Jr; Katherine Gibson; Mousumi Ghosh; Christine Petersen; Douglas E Jones

doi:10.4269/ajtmh.2007.76.669

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Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide

Journal article

Peer reviewed

Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide

Rami M Mukbel, Calvin Patten Jr, Katherine Gibson, Mousumi Ghosh, Christine Petersen and Douglas E Jones

The American journal of tropical medicine and hygiene, Vol.76(4), pp.669-675

04/2007

DOI: 10.4269/ajtmh.2007.76.669

PMID: 17426168

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Abstract

The requirements for effective and efficient intracellular killing of Leishmania amazonensis by activated macrophages are unknown. Despite resistance to the arginase inhibitor LOHA by intracellular L. amazonensis amastigotes, enhanced replication did not account for the relative resistance of this parasite to macrophage activation. Herein we report that the presence of both superoxide and nitric oxide is necessary for efficient killing of L. amazonensis amastigotes within LPS/IFN-gamma-activated bone marrow-derived macrophages generated from C3H mice. Addition of an extracellular signal-regulated kinase (ERK) inhibitor to L. amazonensis-infected macrophages increased the ability of these activated macrophages to kill L. amazonensis amastigotes. This enhanced macrophage killing through addition of ERK inhibitor was abrogated by inhibition of superoxide or iNOS, whereas inhibiting superoxide had no effect on the killing of L. major. These results suggest that ERK activation may modulate effective macrophage killing, leading to the ability of L. amazonensis to resist elimination within activated macrophages.

Cells, Cultured

Extracellular Signal-Regulated MAP Kinases - metabolism

Leishmania - immunology

Mice, Inbred C3H

Macrophages - metabolism

Animals

Superoxides - metabolism

Flavonoids - pharmacology

Mice

Leishmania - growth & development

Nitric Oxide - metabolism

Macrophages - immunology

Nitric Oxide Synthase Type II - metabolism

Details

Title: Subtitle: Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide
Creators: Rami M Mukbel - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011, USA
Calvin Patten Jr
Katherine Gibson
Mousumi Ghosh
Christine Petersen
Douglas E Jones
Resource Type: Journal article
Publication Details: The American journal of tropical medicine and hygiene, Vol.76(4), pp.669-675
DOI: 10.4269/ajtmh.2007.76.669
PMID: 17426168
NLM abbreviation: Am J Trop Med Hyg
ISSN: 0002-9637
eISSN: 1476-1645
Publisher: United States
Grant note: AI48357 / NIAID NIH HHS
Language: English
Date published: 04/2007
Academic Unit: Epidemiology; Pathology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983995113702771

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