title: Role of oxidative stress and apoptosis in the cellular response of murine macrophages upon Leishmania infection.
abstract: 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.
authors: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Wilrijk, Belgium.
authors: Maartje
authors: M
authors: Deschacht
authors: Tim
authors: T
authors: Van Assche
authors: Sarah
authors: S
authors: Hendrickx
authors: Hidde
authors: H
authors: Bult
authors: Louis
authors: L
authors: Maes
authors: Paul
authors: P
authors: Cos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D045744:Cell Line, Tumor; D007896:Leishmaniasis / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D009569:Nitric Oxide