The neutrophil-activating protein of Helicobacter pylori crosses endothelia to promote neutrophil adhesion in vivo.
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.
Polenghi
Alessandra
A
Department of Biology, University of Padua, Padua, Italy.
Bossi
Fleur
F
Fischetti
Fabio
F
Durigutto
Paolo
P
Cabrelle
Anna
A
Tamassia
Nicola
N
Cassatella
Marco A
MA
Montecucco
Cesare
C
Tedesco
Francesco
F
de Bernard
Marina
M
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
D001426:Bacterial Proteins; D018821:CD18 Antigens; D018925:Chemokines; C092412:neutrophil-activating protein A, Helicobacter pylori; D048051:p38 Mitogen-Activated Protein Kinases