title: Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein.
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, Le(b), and the sialyl-Lewis x antigen, sLe(x), 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.
authors.affiliation: Division of Medical Microbiology, Faculty of Health Sciences, Linköping University, 581 85 Linköping, Sweden. chrpe@imk.liu.se
authors.forename: Christoffer
authors.initials: C
authors.lastname: Petersson
authors.forename: Maria
authors.initials: M
authors.lastname: Forsberg
authors.forename: Marina
authors.initials: M
authors.lastname: Aspholm
authors.forename: Farzad O
authors.initials: FO
authors.lastname: Olfat
authors.forename: Tony
authors.initials: T
authors.lastname: Forslund
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
mesh_terms: D018829:Adhesins, Bacterial / Q000633:toxicity*; D001426:Bacterial Proteins / Q000494:pharmacology*; D015536:Down-Regulation; D016480:Helicobacter pylori / Q000737:chemistry*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C500808:SabA protein, Helicobacter pylori; C092412:neutrophil-activating protein A, Helicobacter pylori