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Am J Respir Crit Care Med. 2008 Apr 15;177(8):887-95. doi: 10.1164/rccm.200707-990OC. Epub 2008 Jan 17.

Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumonia.

Author information

1
Section of Infection and Inflammation, School of Medicine and Biomedical Sciences, University of Sheffield, LU107, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK.

Abstract

RATIONALE:

The role of NADPH oxidase activation in pneumonia is complex because reactive oxygen species contribute to both microbial killing and regulation of the acute pulmonary infiltrate. The relative importance of each role remains poorly defined in community-acquired pneumonia.

OBJECTIVES:

We evaluated the contribution of NADPH oxidase-derived reactive oxygen species to the pathogenesis of pneumococcal pneumonia, addressing both the contribution to microbial killing and regulation of the inflammatory response.

METHODS:

Mice deficient in the gp91(phox) component of the phagocyte NADPH oxidase were studied after pneumococcal challenge.

MEASUREMENTS AND MAIN RESULTS:

gp91(phox)(-/-) mice demonstrated no defect in microbial clearance as compared with wild-type C57BL/6 mice. A significant increase in bacterial clearance from the lungs of gp91(phox)(-/-) mice was associated with increased numbers of neutrophils in the lung, lower rates of neutrophil apoptosis, and enhanced activation. Marked alterations in pulmonary cytokine/chemokine expression were also noted in the lungs of gp91(phox)(-/-) mice, characterized by elevated levels of tumor necrosis factor-alpha, KC, macrophage inflammatory protein-2, monocyte chemotactic protein-1, and IL-6. The greater numbers of neutrophils in gp91(phox)(-/-) mice were not associated with increased lung injury. Levels of neutrophil elastase in bronchoalveolar lavage were not decreased in gp91(phox)(-/-) mice.

CONCLUSIONS:

During pneumococcal pneumonia, NADPH oxidase-derived reactive oxygen species are redundant for host defense but limit neutrophil recruitment and survival. Decreased NADPH oxidase-dependent reactive oxygen species production is well tolerated and improves disease outcome during pneumococcal pneumonia by removing neutrophils from the tight constraints of reactive oxygen species-mediated regulation.

PMID:
18202350
PMCID:
PMC2643216
DOI:
10.1164/rccm.200707-990OC
[Indexed for MEDLINE]
Free PMC Article

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