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Infection and Immunity, October 2004, p. 5722-5732, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5722-5732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Neither Neutrophils nor Reactive Oxygen Species Contribute to Tissue Damage during Pneumocystis Pneumonia in Mice

Steve D. Swain,1* Terry W. Wright,2 Peter M. Degel,1 Francis Gigliotti,2 and Allen G. Harmsen1

Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana,1 Departments of Pediatrics and of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York2

Received 16 March 2004/ Returned for modification 13 April 2004/ Accepted 28 June 2004

Neutrophils are implicated in the damage of lung tissue in many disease states, including infectious diseases and environmental insults. These effects may be due to oxidative or nonoxidative functions of the neutrophil or both. We examined the role of neutrophils in pulmonary damage during infection with the opportunistic fungal pathogen Pneumocystis sp. in four mouse models of neutrophil dysfunction. These were (i) a knockout of the gp91phox component of NADPH oxidase, in which reactive oxygen species (ROS) production is greatly reduced; (ii) a double knockout of gp91phox and inducible nitric oxide synthase, in which ROS and nitric oxide production is greatly decreased; (iii) a knockout of the chemokine receptor CXCR2, in which accumulation of intra-alveolar neutrophils is severely diminished; and (iv) antibody depletion of circulating neutrophils in wild-type mice with the monoclonal antibody RB6. Surprisingly, in each case, indicators of pulmonary damage (respiratory rates, arterial oxygen partial pressures, and intra-alveolar albumin concentrations) were the same in knockout mice and comparable wild-type mice. Therefore, whereas neutrophils are a valid correlative marker of lung damage during Pneumocystis infection, neither neutrophils nor ROS appear to be the causative agent of tissue damage. We also show that there is no difference in Pneumocystis burdens between wild-type and knockout mice, which supports the idea that neutrophils do not have a major role in the clearance of this organism.

* Corresponding author. Mailing address: Department of Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717. Phone: (406) 994-7693. Fax: (406) 994-4303. E-mail: uvsss{at}montana.edu.

Editor: T. R. Kozel

Infection and Immunity, October 2004, p. 5722-5732, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.5722-5732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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