Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa

• Published in: The Journal of experimental medicine Vol. 175; no. 2; pp. 517 - 525
• Main Authors: Mai, U E, Perez-Perez, G I, Allen, J B, Wahl, S M, Blaser, M J, Smith, P D
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.02.1992; The Rockefeller University Press
• Subjects: Antibodies, Bacterial - immunology; Bacterial Outer Membrane Proteins - immunology; Bacteriology; Biological and medical sciences; cell surface; chemotaxis; Chemotaxis, Leukocyte - immunology; Fundamental and applied biological sciences. Psychology; gastric mucosa; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; gastritis; Gastritis - immunology; Gastritis - microbiology; Helicobacter Infections - immunology; Helicobacter pylori - enzymology; Helicobacter pylori - immunology; Humans; leucocytes; Microbiology; Monocytes - immunology; N-Formylmethionine Leucyl-Phenylalanine - immunology; Neutrophils - immunology; Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains; proteins; Pyloric Antrum - immunology; Urease - immunology; Human; Biological properties; Spirillales; Digestive system; Leukocyte; Mucosa; Spirillaceae; Lamina propria; Host agent relation; Cell surface; Chemotactic factor; Proteins; Helicobacter pylori; Bacteria
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.175.2.517

The mechanism by which Helicobacter pylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. pylori releases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. pylori whole bacteria or H. pylori-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. pylori urease (a major component of the surface proteins) exhibited dose-dependent, antibody-inhibitable chemotactic activity. In addition, a synthetic 20-amino acid peptide from the NH2-terminal portion of the 61-kD subunit, but not the 30-kD subunit, of urease exhibited chemotactic activity for monocytes and neutrophils, localizing the chemotactic activity, at least in part, to the NH2 terminus of the 61-kD subunit of urease. The ability of leukocytes to chemotax to H. pylori surface proteins despite formyl-methionyl-leucyl-phenylalanine (FMLP) receptor saturation, selective inhibition of FMLP-mediated chemotaxis, or preincubation of the surface proteins with antiserum to FMLP indicated that the chemotaxis was not FMLP mediated. Finally, we identified H. pylori surface proteins and urease in the lamina propria of gastric antra from patients with H. pylori-associated gastritis but not from uninfected subjects. These findings suggest that H. pylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides.