The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor

Citation
B. Satin et al., The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a protective antigen and a major virulence factor, J EXP MED, 191(9), 2000, pp. 1467-1476
Citations number
69
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
00221007 → ACNP
Volume
191
Issue
9
Year of publication
2000
Pages
1467 - 1476
Database
ISI
SICI code
0022-1007(20000501)191:9<1467:TNP(OH>2.0.ZU;2-D
Abstract
Helicobacter pylori infection induces the appearance of inflammatory infilt rates, consisting mainly of neutrophils and monocytes, in the human gastric mucosa. A bacterial protein with neutrophil activating activity (HP-NAP) h as been previously identified, but its role in infection and immune respons e is still largely unknown. Here, we show that vaccination of mice with HP NAP induces protection against H. pylori challenge, and that the majority o f infected patients produce antibodies specific for HP-NAP, suggesting an i mportant role of this factor in immunity. We also show that HP-NAP is chemo tactic for human leukocytes and that it activates their NADPH oxidase to pr oduce reactive oxygen intermediates, as demonstrated by the translocation o f its cytosolic subunits to the plasma membrane, and by the lack of activit y on chronic granulomatous disease leukocytes. This stimulating effect is s trongly potentiated by tumor necrosis factor alpha and interferon gamma and is mediated by a rapid increase of the cytosolic calcium concentration. Th e activation of leukocytes induced by HP-NAP is completely inhibited by per tussis toxin, wortmannin, and PP1. On the basis of these results, we conclu de that HP NAP is a virulence factor important for the H. pylori pathogenic effects at the site of infection and a candidate antigen for vaccine devel opment.