Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo.

Davies, Gareth; Simmonds, Nicola; Stevens, Tim; Sheaff, M.; Banatvala, Nick; Laurenson, Ian F.; Blake, David R.; Rampton, David

doi:10.1136/gut.35.2.179

Cited by 384 publications

(259 citation statements)

References 27 publications

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“…Because large amounts of ROS are released by infected PMNs, the results of this study support the hypothesis that Hp and neutrophils collaborate to induce host tissue damage and ulceration (8,10,12,13). Moreover, it has been suggested that tissue damage allows Hp to acquire critical nutrients (63).…”

Section: Discussionsupporting

confidence: 71%

“…At the same time, the results of several studies indicate that Hp can activate neutrophils in vitro (3)(4)(5)(6)(7)(8). Moreover, neutrophil density in vivo correlates directly with the ability of Hp to cause severe disease (9 -11), and the available data suggest that neutrophils and bacteria act in concert to induce gastric ulceration (8,10,12,13).…”

Section: Helicobacter Pylori Disrupts Nadph Oxidase Targeting In Humamentioning

confidence: 78%

“…5A). Cell activation by HP-NAP and Hp(2-20) is sensitive to PTx and Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) acts via FPRL1 (34). Notably, the fMLP-triggered respiratory burst was efficiently blocked by PTx (4.5 Ϯ 7.8% of control (n ϭ 6)), but responses to Hp were unaffected (103 Ϯ 6% of control (n ϭ 6)).…”

Section: Mechanism Of Hp-induced Superoxide Releasementioning

confidence: 99%

See 2 more Smart Citations

Helicobacter pyloriDisrupts NADPH Oxidase Targeting in Human Neutrophils to Induce Extracellular Superoxide Release

Allen

Beecher

Lynch

et al. 2005

The Journal of Immunology

123

168

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Helicobacter pylori (Hp) infection triggers a chronic influx of polymorphonuclear leukocyte neutrophils (PMNs) into the gastric mucosa. Although Hp reside in a neutrophil-rich environment, how these organisms evade phagocytic killing is largely unexplored. We now show that live Hp (strains 11637, 60190, DT61A, and 11916) are readily ingested by PMNs and induce a rapid and strong respiratory burst that is comparable to PMA. Relative to other particulate stimuli, Hp are more potent activators of PMNs than opsonized zymosan, Staphylococcus aureus, or Salmonella. Strikingly, biochemical and microscopic analyses demonstrate that Hp disrupt NADPH oxidase targeting such that superoxide anions are released into the extracellular milieu and do not accumulate inside Hp phagosomes. Specifically, nascent Hp phagosomes acquire flavocytochrome b558 but do not efficiently recruit or retain p47phox or p67phox. Superoxide release peaks at 16 min coincident with the appearance of assembled oxidase complexes in patches at the cell surface. Oxidant release is regulated by formalin-resistant and heat-sensitive bacterial surface factors distinct from urease and Hp(2–20). Following opsonization with fresh serum, Hp triggers a modest respiratory burst that is confined to the phagosome, and ingested bacteria are eliminated. We conclude that disruption of NADPH oxidase targeting allows unopsonized Hp to escape phagocytic killing, and our findings support the hypothesis that bacteria and PMNs act in concert to damage the gastric mucosa.

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Section: Discussionsupporting

confidence: 71%

Section: Helicobacter Pylori Disrupts Nadph Oxidase Targeting In Humamentioning

confidence: 78%

Section: Mechanism Of Hp-induced Superoxide Releasementioning

confidence: 99%

See 1 more Smart Citation

Helicobacter pyloriDisrupts NADPH Oxidase Targeting in Human Neutrophils to Induce Extracellular Superoxide Release

Allen

Beecher

Lynch

et al. 2005

The Journal of Immunology

123

168

View full text Add to dashboard Cite

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“…Antigenic similarities, 33 cross mimicry with Lewis X antigen, 34 and autoimmune reactions 35 are possible mechanisms of uveitis caused by H. pylori. As the nature of H. pylori stimulating reactive oxygen metabolite production in gastric mucosa, 36,37 oxidative stress in the trabecular meshwork by H. pylori can also induce decreased outflow capacity and increased IOP. With regard to potential autoimmune reactions, H. pylori infection induces humoral and cellular immune responses following activation of macrophages and produces proinflammatory cytokines (including a variety of interleukins).…”

Section: Resultsmentioning

confidence: 99%

The effects of Helicobacter pylori infection on intraocular pressure in anterior uveitis

Kim

Park

Choi

et al. 2012

Eye

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“…Increased levels of ROS in the gastric mucosa have been measured in H. pylori-infected patients (9,10). Exposure of gastric epithelial cells to H. pylori resulted in an inflammatory reaction with production of ROS and nitric oxide (11).…”

mentioning

confidence: 99%

Oxidative Stress-induced Peptidoglycan Deacetylase in Helicobacter pylori

Wang

Olczak

Forsberg

et al. 2009

Journal of Biological Chemistry

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Structural modification of peptidoglycan (PG) is one of the mechanisms that pathogenic bacteria use to evade the host innate immune system. For the noninvasive human gastric pathogen Helicobacter pylori, PG delivery to the host cells is one trigger of the immune response. H. pylori HP310 was markedly up-expressed upon cell exposure to oxidative stress. However, disruption of HP310 did not produce a phenotype distinguishable from the parent, including oxidative stress resistance characteristics. HP310 shows very weak homology to a known gene pgdA encoding PG deacetylase in Streptococcous pneumoniae. PGs from wild type H. pylori and the HP310 mutant were purified and analyzed by matrix-assisted laser desorption ionization time-of-flight and high pressure liquid chromatography. The parent strain PG is partially deacetylated, whereas several major PGdeacetylated muropeptides are absent or significantly reduced in the HP310 mutant. PG deacetylase activity was directly demonstrated by use of pure PG and HP310 protein by measuring the release of acetic acid. The Gram-negative bacterium H. pylori is highly resistant to lysozyme (up to 50 mg/ml), but the HP310 mutant is less resistant to lysozyme compared with the parent strain. Complementation of an hp310 strain with the wild type gene restored lysozyme resistance. The purified PG from the mutant is more susceptible to lysozyme (0.3 mg/ml) digestion than the wild type PG. The PG deacetylation appears to confer lysozyme resistance to escape immune detection. HP310 is representative of a new subfamily of bacterial PG deacetylases.Helicobacter pylori, a pathogenic bacterium infecting over 50% of humans, is the etiological agent for gastritis, peptic ulcer, and gastric cancer (1). H. pylori is highly adapted to its ecologic niche, the human gastric mucosa. The pathogenesis of H. pylori relies on its persistence in surviving a harsh environment, including acidity, peristalsis, and attack by phagocyte cells and their released reactive oxygen species (ROS) 2 (2). H. pylori has a unique array of features that permit entry into the mucus, attachment to epithelial cells, evasion of the immune response, and as a result, persistent colonization and transmission. Numerous virulence factors in H. pylori have been extensively studied, including urease, flagella, BabA adhesin, the vacuolating cytotoxin (VacA), and the cag pathogenicity island (cag-PAI). Peptidoglycan (PG) was found in recent years to be an important factor involved in virulence by pathogenic bacteria (3). PG is one of the main protective barriers in the bacterial cell wall. PG consists of glycan strands made of alternating ␤-1,4-linked N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), which are cross-linked by short peptide chains. In mammalian cells, a group of pattern recognition molecules (Nod1 and Nod2) can sense bacterial PG degradation products (muropeptides), initiating innate immune responses (4, 5). For example, human Nod1 (Toll-like receptor) specifically detects a unique (GlcNAc-MurNAc) tripept...

show abstract

Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo.

Cited by 384 publications

References 27 publications

Helicobacter pyloriDisrupts NADPH Oxidase Targeting in Human Neutrophils to Induce Extracellular Superoxide Release

Helicobacter pyloriDisrupts NADPH Oxidase Targeting in Human Neutrophils to Induce Extracellular Superoxide Release

The effects of Helicobacter pylori infection on intraocular pressure in anterior uveitis

Oxidative Stress-induced Peptidoglycan Deacetylase in Helicobacter pylori

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