title: The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo.
abstract: Helicobacter pylori induces an acute inflammatory response followed by a chronic infection of the human gastric mucosa characterized by infiltration of neutrophils/polymorphonuclear cells (PMNs) and mononuclear cells. The H. pylori neutrophil-activating protein (HP-NAP) activates PMNs, monocytes, and mast cells, and promotes PMN adherence to the endothelium in vitro. By using intravital microscopy analysis of rat mesenteric venules exposed to HP-NAP, we demonstrated, for the first time in vivo, that HP-NAP efficiently crosses the endothelium and promotes a rapid PMN adhesion. This HP-NAP-induced adhesion depends on the acquisition of a high affinity state of beta(2) integrin on the plasma membrane of PMNs, and this conformational change requires a functional p38 MAPK. We also show that HP-NAP stimulates human PMNs to synthesize and release a number of chemokines, including CXCL8, CCL3, and CCL4. Collectively, these data strongly support a central role for HP-NAP in the inflammation process in vivo: indeed, HP-NAP not only recruits leukocytes from the vascular lumen, but also stimulates them to produce messengers that may contribute to the maintenance of the flogosis associated with the H. pylori infection.
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Polenghi
authors.forename: Fleur
authors.initials: F
authors.lastname: Bossi
authors.forename: Fabio
authors.initials: F
authors.lastname: Fischetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Durigutto
authors.forename: Anna
authors.initials: A
authors.lastname: Cabrelle
authors.forename: Nicola
authors.initials: N
authors.lastname: Tamassia
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D018821:CD18 Antigens; D002448:Cell Adhesion; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D007249:Inflammation / Q000209:etiology / Q000382:microbiology; D018375:Neutrophil Activation / Q000276:immunology*; D051381:Rats; D013152:Splanchnic Circulation; D014699:Venules; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D001426:Bacterial Proteins; D018821:CD18 Antigens; D018925:Chemokines; C092412:neutrophil-activating protein A, Helicobacter pylori; D048051:p38 Mitogen-Activated Protein Kinases