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Infection and Immunity, August 2005, p. 4941-4947, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4941-4947.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phagocyte-Derived Reactive Oxygen Species Do Not Influence the Progression of Murine Blood-Stage Malaria Infections

S. M. Potter,1 A. J. Mitchell,1 W. B. Cowden,2 L. A. Sanni,1,{dagger} M. Dinauer,3 J. B. de Haan,4 and N. H. Hunt1*

Molecular Immunopathology Unit, Institute for Biomedical Research, University of Sydney, New South Wales 2006, Australia,1 Immunopathology Group, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia,2 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5225,3 Diabetic Complications Group, Baker Heart Research Institute, Victoria 3181, Australia4

Received 31 May 2004/ Returned for modification 24 August 2004/ Accepted 31 March 2005

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 gp91phox–/– 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 gp91phox–/– 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 gp91phox–/– mice and wild-type mice were not significantly different when they were treated with L-NG-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.

* Corresponding author. Mailing address: Medical Foundation Building (K25), Institute for Biomedical Research, University of Sydney, NSW 2006, Australia. Phone: 61-2-9036-3242. Fax: 61-2-9036-3286. E-mail: nhunt{at}med.usyd.edu.au.

Editor: J. F. Urban, Jr.

{dagger} Present address: Department of Histopathology, Algernon Firth Building, General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, United Kingdom.

Infection and Immunity, August 2005, p. 4941-4947, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4941-4947.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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