The sialic acid binding SabA adhesin of Helicobacter pylori is essential for nonopsonic activation of human neutrophils.

• 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.

Nyckelord

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

1-Phosphatidylinositol 3-Kinase/metabolism

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