The neutrophil-activating protein of Helicobacter pylori

Dundon, William G.; Nishioka, Hiroaki; Polenghi, Alessandra; Papinutto, E.; Zanotti, Giuseppe; Montemurro, P.; Giudice, Giuseppe Del; Rappuoli, Rino; Montecucco, Cesare

doi:10.1078/1438-4221-00165

Cited by 45 publications

(33 citation statements)

References 51 publications

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“…As predicted, CXCL15 expression was upregulated during experimental Helicobacter infection. The function of CXCL15 in this model of inflammation could be to recruit neutrophils because both human and mouse Helicobacter-associated gastritis have a significant neutrophil infiltrate (Dundon et al 2002 and Supplementary Figure 2). In addition, because this model of gastritis progresses over time to gastric adenocarcinoma, it is intriguing to speculate that CXCL15 could also play a role in this progression toward gastric epithelial cancer (Lynch et al 1995;Cahill et al 1996;Nomura et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression of CXCL15 (Lungkine) in Murine Gastrointestinal, Urogenital, and Endocrine Organs

Schmitz

McCracken

Dimmitt

et al. 2007

J Histochem Cytochem.

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S U M M A R Y The ELR1 chemokine CXCL15, which recruits neutrophils during pulmonary inflammation, is also known as lungkine due to its reported exclusive expression in the lung. We now report that CXCL15 mRNA and protein are also expressed in other mucosal and endocrine organs including the gastrointestinal and urogenital tracts and the adrenal gland.Our results indicate that CXCL15 is expressed throughout the gastrointestinal tract, with the exception of the cecum. Gastric CXCL15 protein expression is approximately 10-fold lower than pulmonary expression and primarily occurs in a specific lineage of gastric epithelial cells, the prezymogenic and zymogenic cell. Similar to the increased expression of CXCL15 during pulmonary inflammation, gastric inflammation induced by infection with Helicobacter felis caused an increase in gastric CXCL15 expression. However, colonic CXCL15 expression was not altered in two different models of colonic inflammation, the Helicobacter hepaticus T-cell transfer model and the mdr1a 2/2 model of colitis. These findings clearly demonstrate that CXCL15, previously reported to be the only lung-specific chemokine, is also highly expressed in other murine mucosal and endocrine organs. The functional role of CXCL15 in mucosal disease remains to be elucidated. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.(J Histochem Cytochem 55: [515][516][517][518][519][520][521][522][523][524] 2007)

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Section: Discussionmentioning

confidence: 99%

Expression of CXCL15 (Lungkine) in Murine Gastrointestinal, Urogenital, and Endocrine Organs

Schmitz

McCracken

Dimmitt

et al. 2007

J Histochem Cytochem.

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“…Thus, NapA could be involved in iron sequestering and storage by H. pylori. However, the expression of NapA in H. pylori was shown not to be regulated in response to iron content in the medium nor to play a part in metal resistance of H. pylori; these findings led to the proposal that the primary role of NapA in vivo may not be as an iron binding and storage protein (12,13).…”

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confidence: 98%

Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

et al. 2006

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Neutrophil-activating protein (NapA) has been well documented to play roles in human neutrophil recruitment and in stimulating host cell production of reactive oxygen intermediates (ROI). A separate role for NapA in combating oxidative stress within H. pylori was implied by studies of various H. pylori mutant strains. Here, physiological analysis of a napA strain was the approach used to assess the iron-sequestering and stress resistance roles of NapA, its role in preventing oxidative DNA damage, and its importance to mouse colonization. The napA strain was more sensitive to oxidative stress reagents and to oxygen, and it contained fourfold more intracellular free iron and more damaged DNA than the parent strain. Pure, iron-loaded NapA bound to DNA, but native NapA did not, presumably linking iron levels sensed by NapA to DNA damage protection. Despite its in vitro phenotype of sensitivity to oxidative stress, the napA strain showed normal (like that of the wild type) mouse colonization efficiency in the conventional in vivo assay. By use of a modified mouse inoculation protocol whereby nonviable H. pylori is first inoculated into mice, followed by (live) bacterial strain administration, an in vivo role for NapA in colonization efficiency could be demonstrated. NapA is the critical component responsible for inducing host-mediated ROI production, thus inhibiting colonization by the napA strain. An animal colonization experiment with a mixed-strain infection protocol further demonstrated that the napA strain has significantly decreased ability to survive when competing with the wild type. H. pylori NapA has unique and separate roles in gastric pathogenesis.

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“…H pylori neutrophilactivating protein (HP-NAP), a 150-kDa iron-binding protein, is a ball-shaped dodecamer formed by fourhelix bundled subunits with its sequence similar to that of bacterioferritins and DNA binding proteins [5,6] . It has been designated as a neutrophil-activating factor because it promotes the adherence of neutrophils to endothelial cells and stimulates production of reactive oxygen species (ROS) in neutrophils by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in plasma membrane [7][8][9][10][11] . Satin et al [12] demonstrated that the purified recombinant HP-NAP is chemotactic for human neutrophils and monocytes, induces surface expression of β2-integrin, which mediates endothelial transmigration, adhesion and accumulation of leucocytes at the site of H pylori infection.…”

Section: Introductionmentioning

confidence: 99%

Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer

Long¹,

Luo²,

Li³

et al. 2009

WJG

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AIM: To detect and evaluate the antibodies againstHelicobacter pylori (H pylori ) neutrophil-activating protein (HP-NAP) in patients with gastric cancer and other gastroduodenal diseases. METHODS:Recombinant HP-NAP was prepared from a prokaryotic expression system in Escherichia coli . Serum positivity and level of HP-NAP-specific antibodies in sera from 43 patients with gastric cancer, 28 with chronic gastritis, 28 with peptic ulcer, and 89 healthy controls were measured by rHP-NAP-based ELISA. rHP-NAP-stimulated production of interleukin-8 (IL-8) and growth-related oncogene (GROα) cytokines in the culture supernatant of SGC7901 gastric epithelial cells was also detected. RESULTS:The serum positivity and mean absorbance value of HP-NAP-specific antibodies in the gastric c a n c e r g r o u p ( 9 7.7 % a n d 1 . 0 1 ± 0 . 2 4 ) w e r e significantly higher than those in the chronic gastritis group (85.7% and 0.89 ± 0.14, P < 0.005) and healthy control group (27.7% and 0.65 ± 0.18, P < 0.001). The sensitivity and specificity of ELISA for the detection of HP-NAP-specific antibodies were 95.5% and 91.5%, respectively. HP-NAP could slightly upregulate IL-8 production in gastric epithelial cell lines but had no effect on GROα production. CONCLUSION:Infection with virulent H pylori strains secreting HP-NAP is associated with severe gastroduodenal diseases, and HP-NAP may play a role in the development of gastric carcinoma. rHP-NAPbased ELISA can be used as a new method to detect H pylori infection. The direct effect of HP-NAP on gastric epithelial cells may be limited, but HP-NAP may contribute to inflammatory response or carcinogenesis by activating neutrophils.

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The neutrophil-activating protein of Helicobacter pylori

Cited by 45 publications

References 51 publications

Expression of CXCL15 (Lungkine) in Murine Gastrointestinal, Urogenital, and Endocrine Organs

Expression of CXCL15 (Lungkine) in Murine Gastrointestinal, Urogenital, and Endocrine Organs

Dual Roles of Helicobacter pylori NapA in Inducing and Combating Oxidative Stress

Detection and evaluation of antibodies against neutrophil-activating protein of Helicobacter pylori in patients with gastric cancer

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