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Role of oxidative stress and apoptosis in the cellular response of murine macrophages upon Leishmania infection

Published online by Cambridge University Press:  10 July 2012

MAARTJE DESCHACHT ,
TIM VAN ASSCHE ,
SARAH HENDRICKX ,
HIDDE BULT ,
LOUIS MAES  and
PAUL COS
MAARTJE DESCHACHT
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
TIM VAN ASSCHE
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
SARAH HENDRICKX
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
HIDDE BULT
Affiliation:
Division of Pharmacology, Faculty of Medicine, University of Antwerp, Wilrijk, Belgium
LOUIS MAES
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
PAUL COS*
Affiliation:
Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium
*
*Corresponding author: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Universiteitsplein 1, B-2610 Antwerp, Belgium. Tel: +32 3 265 2628. Fax: +32 3 265 2681. E-mail: paul.cos@ua.ac.be
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Summary

Leishmania parasites are able to survive in the macrophage, one of the most hostile environments of the vertebrate host. The present study investigated how Leishmania infection influences these host cell defence mechanisms. Macrophages were infected with antimony-susceptible and -resistant Leishmania strains. Free radical production in Leishmania-infected macrophages was measured by electron paramagnetic resonance. Apoptosis was detected with fluorescence microscopy using Annexin-V FITC labelling and with Western blotting to detect caspase-3 cleavage. Independent of their drug susceptibility profile or species background, all studied Leishmania strains induced a similar increase in free radical production in macrophages. O2●− production was significantly elevated during phagocytosis of the stationary phase promastigotes. Conversely, NO levels increased later in the infection and none of the strains induced capsase-3 cleavage. Leishmania donovani infection led to phosphatidylserine externalization only in RAW 264.7 cells. After an initial burst of O2●− during phagocytosis of promastigotes, amastigotes protect themselves by decreasing the O2●− production to the basal level. An increased NO production was observed 6 h after infection. Finally, induction of cell death is probably not essential in the survival of the parasite within the macrophage.

Keywords

superoxidenitric oxideEPRapoptosisLeishmania infantumLeishmania donovani
Type
Research Article
Information
Parasitology , Volume 139 , Issue 11 , September 2012 , pp. 1429 - 1437
Copyright
Copyright © Cambridge University Press 2012

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