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.
Highlights
Why The JI? Submit online. Rapid Reviews! 30 days* from submission to initial decision No Triage! Every submission reviewed by practicing scientists Fast Publication! 4 weeks from acceptance to publicatio
Intravital microscopy analysis of rat mesenteric venules exposed to H. pylori neutrophil-activating protein (HP-NAP) for 15 min before image acquisition showed the ability of acridine orange (AO)-labeled leukocytes to adhere to the endothelium
A 150-kDa oligomeric protein isolated from H. pylori water extracts was found to promote neutrophil adhesion to endothelial cells [17, 50], and the protein was named HP-NAP
Summary
PMN, polymorphonuclear cell; AO, acridine orange; HP-NAP, H. pylori neutrophil-activating protein; PAF, platelet-activating factor; PET, polycarbonate; RPA, RNase protection assay; RT, room temperature; VEGF, vascular endothelial growth factor. TNF-␣ can induce activation of integrins on PMNs, directly or by stimulating the secretion of CXCL8 from the endothelium [10, 22] According to these observations, during H. pylori infection it is very likely that HP-NAP, probably together with other bacterial or host-derived factors, may trigger in vivo the PMN accumulation www.jimmunol.org. We demonstrate for the first time that HP-NAP is able to cross the endothelium and to stimulate PMNs to adhere in vivo, in underflow conditions This effect is directly mediated by HP-NAP, which induces a high affinity state of integrins on PMNs, by recruiting a signaling cascade that involves p38-MAPK. We show in this study that HP-NAP up-regulates the mRNA expression and the protein release of several proinflammatory chemokines, including CXCL8, CCL3, and CCL4
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
