The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 1 May 2000.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 168K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Satin, B.
Right arrow Articles by Rossi, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Satin, B.
Right arrow Articles by Rossi, F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2000/5/1467/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 9, May 1, 2000 1467-1476

Original Article

The Neutrophil-Activating Protein (Hp-Nap) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor

Barbara Satina, Giuseppe Del Giudiceb, Vittorina Della Biancac, Stefano Dusic, Carlo Laudannac, Fiorella Tonelloa, Dermot Kelleherd, Rino Rappuolib, Cesare Montecuccoa, and Filippo Rossic

a Centro Consiglio Nazionale Ricerche Biomembrane and Dipartimento di Scienze Biomediche, Università di Padova, 35121 Padova, Italy
b Centro di Ricerche IRIS, Chiron Vaccines Sp.A., 53100 Siena, Italy
c Dipartimento di Patologia Generale, Università di Verona, 37134 Verona, Italy
d Department of Clinical Medicine, Trinity College, Dublin 8, Ireland
Dipartimento di Scienze Biomediche, via G. Colombo n. 3, 35121 Padova, Italy.39-049-827604939-049-8276058

cesare{at}civ.bio.unipd.it

Helicobacter pylori infection induces the appearance of inflammatory infiltrates, consisting mainly of neutrophils and monocytes, in the human gastric mucosa. A bacterial protein with neutrophil activating activity (HP-NAP) has been previously identified, but its role in infection and immune response is still largely unknown. Here, we show that vaccination of mice with HP-NAP induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-NAP, suggesting an important role of this factor in immunity. We also show that HP-NAP is chemotactic for human leukocytes and that it activates their NADPH oxidase to produce reactive oxygen intermediates, as demonstrated by the translocation of its cytosolic subunits to the plasma membrane, and by the lack of activity on chronic granulomatous disease leukocytes. This stimulating effect is strongly potentiated by tumor necrosis factor {alpha} and interferon {gamma} and is mediated by a rapid increase of the cytosolic calcium concentration. The activation of leukocytes induced by HP-NAP is completely inhibited by pertussis toxin, wortmannin, and PP1. On the basis of these results, we conclude 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 development.

Key Words: neutrophils • monocytes • NADPH oxidase • chemotaxis • Helicobacter

Abbreviations used in this paper: [Ca2+]i, intracellular Ca2+ concentration; CGD, chronic granulomatous disease; DPI, diphenyleneiodonium chloride; HP-NAP, Helicobacter pylori neutrophil-activating protein; HRP, horseradish peroxidase; NBT, nitroblue tetrazolium; PI3-K, phosphatidylinositol 3-kinase; PLC, phospholipase C; ROI, reactive oxygen intermediates.

© 2000 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS