title: NADPH oxidase involvement in the pathology of Helicobacter pylori infection.
abstract: Neutrophil oxidants are hypothesized to damage the gastric mucosa and promote carcinogenesis in people infected with Helicobacter pylori. To investigate this process we used wild-type and chronic granulomatous disease (CGD) mice with a targeted disruption of the gp91(phox) subunit of the NADPH oxidase. The mice were inoculated with a mouse-adapted strain of H. pylori and changes in gastric pathology were examined 12 and 30 weeks after infection. Glandular atrophy, a precursor lesion in the development of intestinal-type gastric carcinoma, and epithelial cell proliferation were both dramatically increased in the gastric body of CGD animals within 12 weeks. This correlated strongly with increased numbers of neutrophils in the mucosa (Pearson coefficient 0.97, P < 0.001). H. pylori is a noninvasive bacterium, and there was no increase in bacterial numbers in the CGD animals. Closer examination of the gastric tissue indicated the presence of degenerate neutrophils associated with atrophy. We hypothesize that the release of granule constituents from these neutrophils contributes to tissue damage. This is exacerbated by the absence of a functional NADPH oxidase, and is consistent with this enzyme complex having an important role in dampening the inflammatory response.
authors.affiliation: Department of Surgery, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand.
authors.forename: Jacqueline I
authors.initials: JI
authors.lastname: Keenan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Peterson
authors.forename: Mark B
authors.initials: MB
authors.lastname: Hampton
mesh_terms: D000818:Animals; D016481:Helicobacter Infections / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism*
chemical_list: D019255:NADPH Oxidases