Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP.
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.
Department of Medical Microbiology and Immunology, Göteborg University, Sweden. Mikael.Brisslert@rheuma.gu.se
Mikael
M
Brisslert
Karin
K
Enarsson
Samuel
S
Lundin
Anna
A
Karlsson
Johannes G
JG
Kusters
Ann-Mari
AM
Svennerholm
Steffen
S
Backert
Marianne
M
Quiding-Järbrink
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*
D001426:Bacterial Proteins; D002630:Chemotactic Factors; C092412:neutrophil-activating protein A, Helicobacter pylori