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
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.