The neutrophil-activating protein of Helicobacter pylori (HP-NAP) activates the MAPK pathway in human neutrophils.
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.
Nishioka
Hiroaki
H
Istituto Veneto di Medicina Molecolare, Immunologia Clinica, Università di Padova, Padova, Italy. hiroaki.nishioka@pathology.oxford.ac.uk
Baesso
Ilenia
I
Semenzato
Gianpietro
G
Trentin
Livio
L
Rappuoli
Rino
R
Del Giudice
Giuseppe
G
Montecucco
Cesare
C
D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D037342:Pertussis Toxin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D000199:Actins; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; C092412:neutrophil-activating protein A, Helicobacter pylori; D013481:Superoxides; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one