Abstract
The human pathogen Helicobacter pylori expresses two dominant adhesins; the Lewis b blood group antigen binding adhesin, BabA, and the sialic acid-binding adhesin, SabA. These adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the Lewis b antigen, Leb, and the sialyl-Lewis x antigen, sLex, respectively, which promote infection and inflammatory processes in the gastroduodenal tract. To assess the contribution of each of BabA, SabA and the neutrophil activating protein (HP-NAP) in a local inflammation, we investigated the traits of H. pylori mutants in their capacity to interact with and stimulate human neutrophils. We thence found that the SabA adhesin was not only the key inducer of oxidative metabolism (Unemo et al. J Biol Chem 280:15390–15397, 2005), but also essential in phagocytosis induction, as evaluated by flow cytometry, fluorescence microscopy and luminol-enhanced chemiluminescence. The napA deletion resulted in enhanced generation of reactive oxygen species and impaired adherence to the host cells. In conclusion, the SabA adhesin stimulates human neutrophils through selectin-mimicry. Interestingly, HP-NAP modulates the oxidative burst, which could tune the impact of the H. pylori infection for establishment of balanced and chronic inflammation of the gastric mucosa.
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Acknowledgments
This work was supported by grants from the Program of Infection and Vaccinology (CP/KEM and MA/TB) and the Program of Inflammation (MF), Foundation for Strategic Research (SSF); the ELFA Research Foundation (CP); the Swedish Society for Medical Research (CP); the Swedish Research Council, Project Nos. 621-2001-3570, 521-2001-6565, 11218 (KEM/TB), the King Gustav V 80-Year Foundation (KEM); Swedish Cancer Society, Project No 4101-B00-03XAB (TB); Umeå University Biotechnology Fund (TB), County Council of Västerbotten (TB), the JC Kempe and Seth M Kempe Memorial Foundation (TB), the Mizutani Foundation Glycoscience Award 2003 (TB). We are grateful to Dr. Per-Eric Lindgren for constructive criticism of the material.
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Petersson, C., Forsberg, M., Aspholm, M. et al. Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein. Med Microbiol Immunol 195, 195–206 (2006). https://doi.org/10.1007/s00430-006-0018-x
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DOI: https://doi.org/10.1007/s00430-006-0018-x