Surface Proteins from Helicobacter pylori Exhibit

Stlmnltary The mechanism by which Helicobacter eylori, a noninvasive bacterium, initiates chronic antral gastritis in humans is unknown. We now show that H. Fflori rdeases products with chemotactic activity for monocytes and neutrophils. This chemotactic activity was inhibited by antisera to either H. ~lori whole bacteria or H. pylor/-derived urease. Moreover, surface proteins extracted from H. pylori and purified H. ~lori 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 NHx-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. i;,ylori 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. eylori 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. f,ylori gastritis is initiated by mucosal absorption of urease, which expresses chemotactic activity for leukocytes by a mechanism not involving N-formylated oligopeptides.