title: The neutrophil-activating protein of Helicobacter pylori.
abstract: Infection of the stomach mucosa by the gastric pathogen Helicobacter pylori is accompanied by a large infiltration of neutrophils and monocytes which are believed to contribute substantially to H. pylori-induced gastritis. A protein was identified (HP-NAP for neutrophil-activating protein from H. pylori) that was capable of increasing the adhesion of neutrophils to endothelial cells. We have demonstrated that HP-NAP is a dodecamer composed of identical 17-kDa subunits that induces the production of reactive oxygen radicals (ROIs) by neutrophils via a cascade of intracellular activation events. HP-NAP has also been shown to be chemotactic for neutrophils and monocytes, and a majority of H. pylori-infected patients have been found to produce antibodies specific for HP-NAP making it a strong vaccine candidate. More recently it has been shown that HP-NAP can stimulate tissue factor and plasminogen activator inhibitor-2 production by human monocytes. While structurally similar to the Escherichia coli DNA-binding protein Dps, HP-NAP has characteristics that are more similar to bacterioferritins being capable of binding up to 500 atoms of iron in vitro. Further study, however, has revealed that synthesis of HP-NAP in H. pylori is not altered by the addition or subtraction of metal ions from its growth medium suggesting that the primary role of the protein in vivo is not as a metal-binding protein. A number of other reports have proposed that HP-NAP acts as an adhesin being capable of binding several different compounds in vitro. Sequence analysis of the genomes of several other bacteria reveal that many possess Dps/HP-NAP-like proteins. The preliminary characterisation of some of these proteins will be discussed.
authors.affiliation: Centro CNR Biomembrane e Dipartimento di Scienze Biomediche, Università di Padova, Italy.
authors.forename: William G
authors.initials: WG
authors.lastname: Dundon
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishioka
authors.forename: Alessandra
authors.initials: A
authors.lastname: Polenghi
authors.forename: Elena
authors.initials: E
authors.lastname: Papinutto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanotti
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Montemurro
authors.forename: Giudice Giuseppe
authors.initials: GG
authors.lastname: Del
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002633:Chemotaxis; D004268:DNA-Binding Proteins; D016480:Helicobacter pylori / Q000737:chemistry* / Q000472:pathogenicity; D006801:Humans; D007501:Iron / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C083911:DPS protein, Bacteria; D017382:Reactive Oxygen Species; C092412:neutrophil-activating protein A, Helicobacter pylori; D007501:Iron