title: Phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections.
abstract: Phagocyte-derived reactive oxygen species have been implicated in the clearance of malaria infections. We investigated the progression of five different strains of murine malaria in gp91(phox-/-) mice, which lack a functional NADPH oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. We found that the absence of functional NADPH oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (Plasmodium yoelii and Plasmodium chabaudi K562) or fatal (Plasmodium berghei ANKA, Plasmodium berghei K173 and Plasmodium vinckei vinckei) strains of malaria. This lack of effect was apparent in both primary and secondary infections with P. yoelii and P. chabaudi. There was also no difference in the presentation of clinical or pathological signs between the gp91(phox-/-) or wild-type strains of mice infected with malaria. Progression of P. berghei ANKA and P. berghei K173 infections was unchanged in glutathione peroxidase-1 gene knockout mice compared to their wild-type counterparts. The rates of parasitemia progression in gp91(phox-/-) mice and wild-type mice were not significantly different when they were treated with l-N(G)-methylarginine, an inhibitor of nitric oxide synthase. These results suggest that phagocyte-derived reactive oxygen species are not crucial for the clearance of malaria parasites, at least in murine models.
authors.affiliation: Medical Foundation Building (K25), Institute for Biomedical Research, University of Sydney, NSW 2006, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Potter
authors.forename: A J
authors.initials: AJ
authors.lastname: Mitchell
authors.forename: W B
authors.initials: WB
authors.lastname: Cowden
authors.forename: L A
authors.initials: LA
authors.lastname: Sanni
authors.forename: M
authors.initials: M
authors.lastname: Dinauer
authors.forename: J B
authors.initials: JB
authors.lastname: de Haan
authors.forename: N H
authors.initials: NH
authors.lastname: Hunt
mesh_terms: D000818:Animals; D018450:Disease Progression; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007107:Immune System / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism*; D010962:Plasmodium berghei / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D017382:Reactive Oxygen Species; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D000094765:Glutathione Peroxidase GPX1