The sialic acid binding SabA adhesin of Helicobacter pylori is essential for nonopsonic activation of human neutrophils.
2005 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 280, no 15, 15390-15397 p.Article in journal (Refereed) Published
Infiltration of neutrophils and monocytes into the gastric mucosa is a hallmark of chronic gastritis caused by Helicobacter pylori. Certain H. pylori strains nonopsonized stimulate neutrophils to production of reactive oxygen species causing oxidative damage of the gastric epithelium. Here, the contribution of some H. pylori virulence factors, the blood group antigen-binding adhesin BabA, the sialic acid-binding adhesin SabA, the neutrophil-activating protein HP-NAP, and the vacuolating cytotoxin VacA, to the activation of human neutrophils in terms of adherence, phagocytosis, and oxidative burst was investigated. Neutrophils were challenged with wild type bacteria and isogenic mutants lacking BabA, SabA, HP-NAP, or VacA. Mutant and wild type strains lacking SabA had no neutrophil-activating capacity, demonstrating that binding of H. pylori to sialylated neutrophil receptors plays a pivotal initial role in the adherence and phagocytosis of the bacteria and the induction of the oxidative burst. The link between receptor binding and oxidative burst involves a G-protein-linked signaling pathway and downstream activation of phosphatidylinositol 3-kinase as shown by experiments using signal transduction inhibitors. Collectively our data suggest that the sialic acid-binding SabA adhesin is a prerequisite for the nonopsonic activation of human neutrophils and, thus, is a virulence factor important for the pathogenesis of H. pylori infection.
Place, publisher, year, edition, pages
2005. Vol. 280, no 15, 15390-15397 p.
1-Phosphatidylinositol 3-Kinase/metabolism, Adhesins; Bacterial/chemistry/metabolism/*physiology, Animals, Bacterial Adhesion, Bacterial Proteins/chemistry, Chromatography; High Pressure Liquid, Chromatography; Thin Layer, Cytotoxins/chemistry, Electrophoresis; Polyacrylamide Gel, Granulocytes/metabolism, Helicobacter pylori/*metabolism, Humans, Hydrogen Peroxide/pharmacology, Magnetic Resonance Spectroscopy, N-Acetylneuraminic Acid/*metabolism, Neutrophils/chemistry/*metabolism/*microbiology, Oligonucleotides/chemistry, Oxidative Stress, Phagocytosis, Protein Binding, Reactive Oxygen Species, Respiratory Burst, Signal Transduction, Time Factors
IdentifiersURN: urn:nbn:se:umu:diva-6647DOI: 10.1074/jbc.M412725200PubMedID: 15689619OAI: oai:DiVA.org:umu-6647DiVA: diva2:146317