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.

Nyckelord

Bacterial Proteins/genetics/*metabolism/pharmacology

Cells

Cultured

Chemotactic Factors/genetics/metabolism/pharmacology

Chemotaxis

Leukocyte/*drug effects

Endothelial Cells/*immunology

Endothelium

Vascular/cytology/immunology

Helicobacter pylori/genetics/*immunology/metabolism

Humans

Neutrophil Activation/immunology

Neutrophils/*immunology

Research Support

Non-U.S. Gov't

Publikations- och innehållstyp

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