Surface proteins from Helicobacter pylori exhibit chemotactic activity for human leukocytes and are present in gastric mucosa.
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.
Mai
U E
UE
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Perez-Perez
G I
GI
Allen
J B
JB
Wahl
S M
SM
Blaser
M J
MJ
Smith
P D
PD
D000907:Antibodies, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology*; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011706:Pyloric Antrum / Q000276:immunology; D014510:Urease / Q000276:immunology
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014510:Urease