The Role of Neutrophil Activation in Pathogenesis of Preeclampsia

To investigate the effect of neutrophil activation on pathogenesis of pre eclampsia, neutrophil activation was examined by using flow cytometry to assess the CD11b expression and the levels of plasma endothelin 1 (ET 1) and serum NO - 2 were also measured by using non equilibrium radioimmunoassay and by Griess assay in 29 pregnant women with pre eclampsia and 31 normal pregnant women at third trimester. The expression of neutrophil CD11b was significantly elevated in women with pre eclampsia as compared with that of normal pregnant women at third trimester. The mean fluorescence index of CD11b was 438.38±179.91 and 326.97±170.14 respectively ( P < 0.05). The plasma ET 1 level and serum NO 2 concentration in pre eclampsic women (63.69±48.33 pg/ml and 20.03±4.77 μmol/L, respectively) were both significantly increased as compared with those in the normal pregnancy women (29.98±20.25 pg/ml and 15.47±5.47 μmol/L, respectively, P <0.01). The neutrophil CD11b expression was significantly elevated in pre eclampsia. The increased neutrophil activation may cause the damage of vascular endothelium and result in NO release compensatory increase in endothelial cells, suggesting that the neutrophil activation may play a key role in pathogenesis of pre eclampsia.

Helicobacter pylori neutrophil activating protein as target for new drugs against H.pylori inflammation

Helicobacter pylori(H.pylori) infection is among the most common human infections and the major risk factor for peptic ulcer disease and gastric cancer.With-in this work we present the implication of C-terminal region of H.pylori neutrophil activating protein in the stimulation of neutrophil activation as well as the evi-dence that the C-terminal region of H.pylori activating protein is indispensable for neutrophil adhesion to endothelial cells,a step necessary to H.pylori inflammation.In addition we show that arabino galactan proteins derived from chios mastic gum,the natural resin of the plant Pistacia lentiscus var.Chia inhibit neutrophil activation in vitro.

Construction of an oral recombinant DNA vaccine from H pylori neutrophil activating protein and its immunogenicity

AIM： To construct a live attenuated Salmonella typhimurium （S. typhimurium） strain harboring the H pylori neutrophil activating protein （HP-NAP） gene as an oral recombinant DNA vaccine, and to evaluate its immunogenicity. METHODS： By genetic engineering methods, the genomic DNA of Hpylori was extracted as a template. The total length of the HP-NAP gene was amplified by polymerase chain reaction （PCR） and cloned into pBT vector for sequencing and BLAST analysis, then subcloned into a eukaryotic expression vector pIRES followed by PCR identification and restriction enzyme digestion. The identified recombinant plasmid pIRES-NAP was transfected into COS-7 cells for target fusion protein expression, and its antigenicity was detected by Western blotting. Then the recombinant plasmid was transformed into a live attenuated S. typhimurium strain SL7207 as an oral vaccine strain, and its immunogenicity was evaluated with animal experiments. RESULTS： A 435 bp product was cloned using high homology with HP-NAP gene in GenBank （more than 98%）. With identification by PCR and restriction enzyme digestion, a recomoinant eukaryotic expression plasmid pIRES-NAP containing the HP-NAP gene of H pylori was successfully constructed. The expressed target protein had a specific reaction with Hpyloril whole cell antibody and showed a single strip result detected by Western blotting. Oral immunization of mice with recombinant DNA vaccine strain SL7207 （pIRES-NAP） also induced a specific immune response. CONCLUSION： The successful construction of HP-NAP oral DNA vaccine with good immunogenicity may help to further investigate its immunoprotection effects and develop vaccine against Hpylori infection.

Endoscopy-based Kyoto classification score of gastritis related to pathological topography of neutrophil activity

BACKGROUND Endoscopy-based Kyoto classification for gastritis and pathological topographic distribution of neutrophil infiltration are correlated with gastric cancer risk.AIM To investigate the association between Kyoto classification and the topographic distribution of neutrophil activity.METHODS Kyoto classification score,ranging from 0 to 8,consisted of atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness.Neutrophil activity was scored according to the updated Sydney System using biopsy samples obtained from the greater curvature of the corpus and the antrum.The participants were divided into four categories,inactive stomach,antrumpredominant gastritis,pangastritis,and corpus-predominant gastritis,based on the topographic distribution of neutrophil activity.Effects of sex,age,body mass index,drinking habit,smoking habit,family history of gastric cancer,serum Helicobacter pylori(H.pylori)antibody,and Kyoto score on topography of neutrophil infiltration were analyzed.RESULTS A total of 327 patients(comprising 50.7%women,with an average age of 50.2 years)were enrolled in this study.H.pylori infection rate was 82.9%with a mean Kyoto score of 4.63.The Kyoto score was associated with the topographic distribution of neutrophil activity.Kyoto scores were significantly higher in the order of inactive stomach,antrum-predominant gastritis,pangastritis,and corpuspredominant gastritis(3.05,4.57,5.21,and 5.96,respectively).Each individual score of endoscopic findings(i.e.,atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness)was correlated with the topographic distribution of neutrophil activity.On multivariate analysis,the Kyoto score,age,and serum H.pylori antibody were independently associated with the topographic distribution of neutrophil activity.CONCLUSION The Kyoto classification score was associated with the topographic distribution of neutrophil activity.

Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections

Repetitive implant-related infections(IRIs)are devastating complications in orthopedic surgery,threatening implant survival and even the life of the host.Biofilms conceal bacterial-associated antigens(BAAs)and result in a"cold tumor"-like immune silent microenvironment,allowing the persistence of IRIs.To address this challenge,an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum(CFCP)was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response.Specifically,enhanced sonodynamic therapy(SDT)from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA(dsDNA).Immunogenic dsDNA promoted dendritic cell(DC)maturation through activation of the stimulator of interferon gene(STING)and amplified the immune stimulation of neutrophils via interferon-β(IFN-β).At the same time,enhanced BAA presentation aroused humoral immunity in B and T cells,creating long-term resistance to repetitive infections.Encouragingly,CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.