Helicobacter pylori induce neutrophil transendothelial migration: Role of the bacterial HP-NAP

• Published in: FEMS microbiology letters Vol. 249; no. 1; pp. 95 - 103
• Main Authors: Brisslert, Mikael, Enarsson, Karin, Lundin, Samuel, Karlsson, Anna, Kusters, Johannes G., Svennerholm, Ann-Mari, Backert, Steffen, Quiding-Järbrink, Marianne
• Format: Journal Article
• Language: English
• Published: Oxford, UK Elsevier B.V 01.08.2005; Blackwell Publishing Ltd; Blackwell
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Bacteriology; Biological and medical sciences; Cells, Cultured; Chemotactic Factors - genetics; Chemotactic Factors - metabolism; Chemotactic Factors - pharmacology; Chemotaxis, Leukocyte - drug effects; Endothelial cells; Endothelial Cells - immunology; Endothelium, Vascular - cytology; Endothelium, Vascular - immunology; Fundamental and applied biological sciences. Psychology; Genetics; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - immunology; Helicobacter pylori - metabolism; HP-NAP; Humans; Inflammation; Microbiology; Neutrophil Activation - immunology; Neutrophils - immunology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; Transmigration; HP-NAP; Transmigration; Inflammation; Helicobacter pylori; Endothelial cells; Endothelial cell; Statistical analysis; Spirillales; Spirillaceae; Protein; Gastritis; Mutagenesis; Bacteria; Neutrophil; Microaerophily
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1016/j.femsle.2005.06.008

Continuous recruitment of neutrophils into the inflamed gastric mucosal tissue is a hallmark of Helicobacter pylori infection in humans. In this study, we examined the ability of H. pylori to induce transendothelial migration of neutrophils using a transwell system consisting of a cultured monolayer of human endothelial cells as barrier between two chambers. We showed for the first time that live H. pylori, but not formalin-killed bacteria, induced a significantly increased transendothelial migration of neutrophils. H. pylori conditioned culture medium also induced significantly increased transendothelial migration, whereas heat-inactivated culture filtrates had no effect, suggesting that the chemotactic factor was proteinaceous. Depletion of H. pylori-neutrophil activating protein (HP-NAP) from the culture filtrates resulted in significant reduction of the transmigration. Culture filtrates from isogenic HP-NAP deficient mutant bacteria also induced significantly less neutrophil migration than culture filtrates obtained from wild-type bacteria. HP-NAP did not induce endothelial cell activation, suggesting that HP-NAP acts directly on the neutrophils. In conclusion, our results demonstrate that secreted HP-NAP is one of the factors resulting in H. pylori induced neutrophil transendothelial migration. We propose that HP-NAP contributes to the continuous recruitment of neutrophils to the gastric mucosa of H. pylori infected individuals.