The neutrophil-activating protein of Helicobacter pylori (HP-NAP) activates the MAPK pathway in human neutrophils

Eur J Immunol. 2003 Apr;33(4):840-9. doi: 10.1002/eji.200323726.


Infection by Helicobacter pylori causes an acute inflammatory response followed by a chronic infection of the human gastric mucosa characterized by the infiltration of neutrophils andmononuclear inflammatory cells. The neutrophil-activating protein of Helicobacter pylori (HP-NAP) is a virulence factor that activates neutrophils, monocytes, and mast cells. However, the mechanism by which HP-NAP activates these cells is not fully understood. Here, we show that HP-NAP induces extracellular regulated kinase (ERK) and p38-mitogen-activated protein kinase (MAPK) activation in human neutrophils; c-Jun N-terminal kinase is not activated by HP-NAP. A MAPK/ERK kinase inhibitor and a p38-MAPK inhibitor suppress HP-NAP-mediated neutrophil oxidative burst, adhesion, andchemotaxis, but not actin polymerization. Pertussis toxin (PTX) inhibits all these neutrophil functions and the MAPK activation caused by HP-NAP. These results demonstrate that HP-NAP activates neutrophils through a PTX-sensitive pathway and that ERK and p38-MAPK are involved in many neutrophil functions stimulated by HP-NAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • Cell Adhesion / drug effects
  • Chemotaxis, Leukocyte / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • MAP Kinase Signaling System* / drug effects
  • Mitogen-Activated Protein Kinases* / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases* / metabolism*
  • Neutrophils / drug effects
  • Neutrophils / enzymology*
  • Neutrophils / immunology
  • Pertussis Toxin / pharmacology
  • Pyridines / pharmacology
  • Superoxides / metabolism


  • Actins
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Pyridines
  • neutrophil-activating protein A, Helicobacter pylori
  • Superoxides
  • Pertussis Toxin
  • Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one