bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages
Authors: Soehnlein O , Kenne E , Rotzius P , Eriksson E E , Lindbom L 
Published: July 2010

SummaryMacrophages represent a multi-functional cell type in innate immunity that contributes to bacterial clearance by recognition, phagocytosis and killing. In acute inflammation, infiltrating neutrophils release a wide array of preformed granule proteins which interfere functionally with their environment. Here, we present a novel role for neutrophil-derived granule proteins in the anti-microbial activity of macrophages. Neutrophil secretion obtained by antibody cross-linking of the integrin subunit CD18 (X-link secretion) or by treatment with N-Formyl-Met-Leu-Phe (fMLP secretion) induced a several-fold increase in bacterial phagocytosis by monocytes and macrophages. This response was associated with a rapid activation of the monocytes and macrophages as depicted by an increase in cytosolic free Ca2+. Interestingly, fMLP secretion had a more pronounced effect on monocytes than the X-link secretion, while the opposite was observed for macrophages. In addition, polymorphonuclear cells (PMN) secretion caused a strong enhancement of intracellular reactive oxygen species (ROS) formation compared to incubation with bacteria. Thus, secretion of neutrophil granule proteins activates macrophages to increase the phagocytosis of bacteria and to enhance intracellular ROS formation, indicating pronounced intracellular bacterial killing. Both mechanisms attribute novel microbicidal properties to PMN granule proteins, suggesting their potential use in anti-microbial therapy.
Glabridin, a functional compound of liquorice, attenuates colonic inflammation in mice with dextran sulphate sodium-induced colitis
Authors: Kwon H-S , Oh S-M , Kim J-K 
Published: July 2010

Summary
Inflammatory bowel disease (IBD) is characterized by detrimental immune reactivity in the gut, and the imbalance between proinflammatory and anti-inflammatory reactivity. The aims of this study were to determine whether oral administration of glabridin, a functional component of liquorice, could ameliorate dextran sulphate sodium (DSS)-induced colitis, as well as to understand the possible underlying mechanisms. Acute experimental colitis was induced in BALB/c mice by treatment with 5% DSS for 7 days. Glabridin (10 or 50 mg/kg/day) was given for 7 days. Treatment with glabridin significantly attenuated mortality, loss of body weight, shortening of the colon and severe clinical symptoms. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E2, and proinflammatory cytokines. These results suggest that glabridin-mediated anti-inflammatory action on colorectal sites may be a useful therapeutic approach to IBD.
Maternal and neonatal lipopolysaccharide and Fas responses are altered by antenatal risk factors for sepsis
Authors: Molloy E J , O'Neill A J , Grantham-Sloan J J , Webb D W , Watson R W G 
Published: July 2010

Summary
The diagnosis of neonatal sepsis is difficult, resulting in unnecessary treatment to minimize morbidity and mortality. We hypothesized that exposure to antenatal risk factors for sepsis alters the perinatal neutrophil phenotype. The study setting was a tertiary referral university-affiliated maternity and neonatal hospital. Neutrophils from adults, normal neonates, neonates with antenatal sepsis risk factors and their respective maternal samples were incubated alone, with agonistic Fas antibody or with lipopolysaccharide (LPS). Surface receptor CD11b expression and the percentage apoptosis (persistent inflammatory response) were assessed using flow cytometry. Both mothers and asymptomatic neonates exposed to maternal sepsis risk factors had increased spontaneous neutrophil apoptosis compared to their respective controls. Infants with sepsis were LPS and Fas hyporesponsive. Maternal neutrophils had a delay in apoptosis in all groups with enhanced LPS and Fas responses associated with neonatal sepsis. CD11b expression was not altered significantly between groups. Maternal neutrophil function is altered in neonatal sepsis and may have a diagnostic role. Neonatal sepsis was associated with LPS hyporesponsiveness, potentially increasing susceptibility to infection.
Levamisole enhances immune response by affecting the activation and maturation of human monocyte-derived dendritic cells
Authors: Chen L-Y , Lin Y-L , Chiang B-L 
Published: July 2010

SummaryLevamisole is a synthetic phenylimidazolthiazole that was first introduced in 1966 as an anti-helmintic agent. Current studies have been focused upon its effect on immune response and on cancer treatment. We examined the molecular mechanisms of levamisole in the activation and maturation of human monocyte-derived dendritic cells (DC) and human T cells. Treatment of DC with levamisole increased the presentation of CD80, CD86, CD83 and human leucocyte antigen D-related (HLA-DR) molecules on the cell membrane, as well as the production of interleukin (IL)-12 p40 and IL-10. Levamisole-treated human DC also enhanced T cell activation towards type 1 T helper immune response by inducing interferon-γ secretion. Neutralization with antibodies against Toll-like receptor (TLR)-2 inhibited levamisole-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-2 in signalling DC upon incubation with levamisole. The inhibition of nuclear factor-κB, extracellular signal-regulated kinases 1/2 or c-Jun N-terminal kinases pathways also prevented the effects of levamisole on DC in producing IL-12 p40 or IL-10. Taken together, levamisole could enhance immune response towards T helper 1 development through the activation of dendritic cells or T cell aspects.
Development of time-resolved immunofluorometric assays for vascular endothelial growth factor and application on plasma of patients with gastric tumours
Authors: Sheng S L , Bao S H , Huang G , Wang L M 
Published: July 2010

Summary
A highly sensitive and accurate time-resolved immunofluorometric assay (TR-IFMA) has been developed, for the first time, to measure plasma vascular endothelial growth factor (VEGF) in patients with gastric tumours. A monoclonal anti-hVEGF antibody and a biotinylated anti-hVEGF antibody were used to develop a non-competitive ‘sandwich’-type assay. Fluorescence can be measured by a time-resolved fluorometer after binding of europium (Eu)3+-labelled streptavidin to the biotinylated immunoglobulin. Plasma VEGF concentrations were measured by TR-IFMA in 92 healthy controls, in 36 benign stomach disease patients and in 92 gastric cancer patients before surgery. The association between plasma VEGF levels and clinicopathological features was evaluated. A standard curve for VEGF TR-IFMA has been developed with good sensitivity (0·37 pg/ml). Accuracy studies, specificity, parallelism and precision data were determined and all were found to be satisfactory. The validity of the VEGF assay was confirmed by the good correlation between the results obtained by TR-IFMA and commercial enzyme-linked immunosorbent assay (ELISA) (ELISA result = 1·862 + 0·953 (TR-IFMA result), r = 0·944]. The plasma levels of VEGF are higher in gastric cancer patients than in healthy controls. VEGF levels were associated significantly with the presence of distant metastases, as well as invasion depth of the tumour and tumour stage, but not with tumour location, tumour histology, differentiation or the presence of lymph node metastases. At the cut-off of 217·79 pg/ml, the diagnostic sensitivity, specificity and accuracy of the TR-IFMA were 40·2%, 93·7% and 69·9%, respectively. A highly sensitive and reliable TR-IFMA for VEGF has been developed. The determination of plasma VEGF levels may be clinically useful.
Serial lung function tests in primary immune deficiency
Authors: Rich A L , Le Jeune I R , McDermott L , Kinnear W J M 
Published: July 2010

Summary
Pulmonary complications are common in patients with primary immune deficiency (PID). The aim of this study was to assess the usefulness of lung function tests (LFTs) in the management of these patients, and in particular to see if carbon monoxide transfer factor (TLCO) is needed in addition to spirometry. We studied 20 patients (11 female) with PID in a tertiary referral clinic, with a mean age of 47·6 years. Serial LFTs, spanning a mean of 101 months, were correlated with immunoglobulin levels and antibiotic usage. Seven patients showed a decline in forced expiratory volume in 1 second over the period of the study. An additional five patients showed a decline in TLCO. Of these 12 patients, two had no radiographic evidence of lung disease. Higher levels of immunoglobulin were associated with slower decline in LFTs (P &lt; 0·05). The analysis of antibiotic usage and LFTs failed to show a statistically significant effect, although there was a trend towards a slower rate of decline with greater use of antibiotics. LFTs decline slowly in patients with PID. Annual testing (both spirometry and transfer factor) is useful in the assessment of these patients, and should not be confined to those with radiological evidence of lung disease.
Long-term interleukin-10 presence induces the development of a novel, monocyte-derived cell type
Authors: Schoenbein C , Docke W-D , Wolk K , Belbe G , Hoflich C , Jung M , Grutz G , Sterry W , Volk H-D , Asadullah K , Sabat R 
Published: July 2010

SummaryInterleukin (IL)-10 is one of the most crucial immunoregulatory cytokines. Its short-term effects have been analysed extensively, but little is known about its long-term effects. This is of considerable importance, as high systemic IL-10 levels are present for long periods in patients with persistent viral infections, certain cancers and in critical care patients. Our study investigated the effects of the long-term presence of IL-10 on human peripheral blood monocytes. In vitro, IL-10 treatment of these cells for 7 days induced the development of a novel cell type characterized by unique phenotypical and functional characteristics. These cells showed high HLA-DR expression and low expression of CD86 and other co-stimulatory molecules on their surface. The mRNA levels of both HLA-DR and CD86 were high, but no intracellular accumulation of CD86 protein was observed. With respect to its function, these cells showed strongly diminished tumour necrosis factor-α production following lipopolysaccharide stimulation, strongly diminished allogenic CD4+ T cell stimulatory capacity, and even induced a hyporesponsive state in CD4+ T cells. The phenotype remained stable despite the removal of IL-10. In vivo, we found monocytic cells from patients exhibiting this phenotype after long-term IL-10 exposure. These results complement our knowledge further about the biological effects of IL-10 and may provide an explanation for the sustained immunodeficiency in cases of the persistent presence of systemic IL-10.
Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells
Authors:   The Finnish Multiple Sclerosis and Pregnancy Study Group, Airas L , Saraste M , Rinta S , Elovaara I , Huang Y-H , Wiendl H 
Published: July 2010

SummaryMultiple sclerosis (MS) ameliorates typically during pregnancy but after the delivery the relapse rate often increases. Our study was conducted to understand the immunoregulatory mechanisms accompanying this phenomenon. MS patients were followed-up prospectively during pregnancy and 6 months postpartum, with immunological characterization of the peripheral blood. Groups of age- and parity-matched healthy pregnant women, and age- and sex-matched non-pregnant women and non-pregnant MS patients were studied as controls. In our patient cohort, the annualized relapse rate was 1·0 ± 1·0 relapses/woman/year (mean ± standard deviation) during the year before pregnancy, but dropped to 0·2 ± 0·9 during the third trimester (P = 0·02). After the delivery the relapse rate increased again to 1·4 ± 1·9 (1–3 months postpartum versus third trimester P = 0·003). While percentages of peripheral blood CD3, CD4, CD8 and CD19 immune cell subsets were unchanged over the observation period, reduced disease activity during the last trimester was associated with a significant increase in the percentage of circulating CD56bright natural killer (NK) cells. Simultaneously, the proportion of circulating CD56dim NK cells was clearly reduced. No alteration was noted in CD4+ CD25high forkhead box P3+ regulatory T cells. Production of interferon-gamma by peripheral blood lymphocytes was down-regulated significantly during pregnancy in comparison to the postpartum period, resulting in an increased T helper type 2 (Th2) : Th1 ratio during pregnancy. In conclusion, pregnant state in MS patients is characterized by an increase in the percentage of CD56bright NK cells and by enhanced Th2 type cytokine secretion. Our findings suggest a potential role for CD56bright regulatory NK cells in the control of autoimmune inflammation during pregnancy in MS.
High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality
Authors: Johansen J S , Pedersen A N , Schroll M , Jørgensen T , Pedersen B K , Bruunsgaard H 
Published: July 2010

SummaryYKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18–30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 μg/l, P &lt; 0·0005). Serum YKL-40 correlated with serum IL-6 in elderly women (Spearman's rho = 0·30, P = 0·009) and men (rho = 0·25, P = 0·003), but only with serum TNF-α (rho = 0·23, P = 0·05) and C-reactive protein (CRP) (rho = 0·57, P &lt; 0·0005) among the elderly women. In addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2·38, 95% confidence interval (CI): 1·19–4·78, P = 0·02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti-inflammatory medicine). These results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all-cause mortality in octogenarians.
Up-regulation of the phosphoinositide 3-kinase pathway in human lamina propria T lymphocytes
Authors: Braunstein J , Autschbach F , Giese T , Lasitschka F , Heidtmann A , Sido B , Funke B , Reiser C , Schröder A J , Nebl G , Samstag Y , Meuer S C 
Published: July 2010

SummaryHuman intestinal lamina propria T lymphocytes (LPT), when investigated ex vivo, exhibit functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). One prominent feature represents their enhanced sensitivity to CD2 stimulation when compared to PBT. Given that LPT are hyporesponsive to T cell receptor (TCR)/CD3 stimulation, an alternative activation mode, as mimicked by CD2 triggering in vitro, may be functional in mucosal inflammation in vivo. This study provides insight into signalling events associated with the high CD2 responsiveness of LPT. When compared to PBT, LPT show an increased activation of the phosphoinositide 3/protein kinase B/glycogen synthase kinase 3β (PI3-kinase/AKT/GSK-3β) pathway in response to CD2 stimulation. Evidence is provided that up-regulation of this pathway contributes to the enhanced CD2-induced cytokine production in LPT. Given the importance of TCR-independent stimulation for the initiation of intestinal immune responses analysis of signalling pathways induced by ‘co-stimulatory’ receptors may provide valuable information for therapeutic drug design.
Leptin promotes cell survival and activates Jurkat T lymphocytes by stimulation of mitogen-activated protein kinase
Authors: Fernández-Riejos P , Goberna R , Sánchez-Margalet V 
Published: July 2010

SummaryLeptin (Ob) is a non-glycosylated peptide hormone that regulates energy homeostasis centrally, but also has systemic effects including the regulation of the immune function. We have reported previously that leptin activates human peripheral blood lymphocytes co-stimulated with phytohaemagglutinin (PHA) (4 μg/ml), which prevented the employment of pharmacological inhibitors of signalling pathways. In the present study, we used Jurkat T cells that responded to leptin with minimal PHA co-stimulation (0·25 μg/ml). The long isoform of leptin receptor is expressed on Jurkat T cells and upon leptin stimulation, the expression of early activation marker CD69 increases in a dose-dependent manner (0·1–10 nM). We have also found that leptin activates receptor-associated kinases of the Janus family-signal transucers and activators of transcription (JAK-STAT), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) signalling pathways. Moreover, we sought to study the possible effect of leptin on cell survival and apoptosis of Jurkat T cells by culture in serum-free conditions. We have assayed the early phases of apoptosis by flow cytometric detection of fluorescein isothiocyanate (FITC)-labelled annexin V simultaneously with dye exclusion of propidium iodide (PI). As well, we have assayed the activation level of caspase-3 by inmunoblot with a specific antibody that recognizes active caspase-3. We have found that leptin inhibits the apoptotic process dose-dependently. By using pharmacological inhibitors, we have found that the stimulatory and anti-apoptotic effects of leptin in Jurkat T cells are dependent on MAPK activation, rather than the PI3K pathway, providing new data regarding the mechanism of action of leptin in T cells, which may be useful to understand more clearly the association between nutritional status and the immune function.
Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-α levels in Asian Indians
Authors: Sharma S , Ghosh B , Sharma S K 
Published: July 2010

Summary
Tumour necrosis factor (TNF)-α, an important proinflammatory cytokine, has been implicated in the pathogenesis of sarcoidosis, a multi-systemic granulomatous disorder of unknown aetiology. Here, we report for the first time the association of TNF haplotypes and genotypes with sarcoidosis and its prognosis in the Indian population. Five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene were genotyped in a clinically well-defined cohort of North-Indian patients with sarcoidosis (n = 96) and their regional controls (n = 155). Serum TNF-α (sTNF-α) and serum angiotensin converting enzyme (SACE) levels were measured and correlated with genotypes and haplotypes. The TNFA_-1031 and TNFA_-863 polymorphisms were identified as markers for disease onset (FET P = 0·006 and 0·042 for TNFA_-1031 and TNFA_-863, respectively). Additionally, the allele A of LTA_NcoI polymorphism was shown to be prevalent in the ‘no treatment’ group (FET P = 0·005), while the G allele was associated with frequent relapses on drug withdrawal (P = 0·057). Furthermore, the TNFA-308G&gt;A and the TNFA-238G&gt;A polymorphisms were found to influence sTNF-α (P = 0·054 and 0·0005, respectively) and SACE levels (P = 0·0017 and 0·056, respectively). The haplotype frequencies were significantly different in the patients and the controls (P = 0·0067). The haplotype GTCCGG was identified as the major risk/susceptibility haplotype (P = 0·003) and was associated with increased SACE levels in the patient population. In conclusion, our study suggests an association of TNF polymorphisms with sarcoidosis.
Multiple-antigen immunization of chickens facilitates the generation of recombinant antibodies to autoantigens
Authors: Hof D , Hoeke M O , Raats J M H 
Published: July 2010

SummaryAntibody phage display is a powerful tool for the generation of monoclonal antibodies against virtually any given antigen. Chickens are phylogenetically more distant from humans compared to other laboratory animals, such as mice and rats. Therefore, the use of chickens is especially beneficial when generating recombinant antibodies against human autoantigens, which are often highly conserved among mammals. Another advantage of using chickens in antibody phage display is that the preparation of single chain variable fragment (scFv) antibody libraries is faster and easier compared to preparing such libraries from other species, as only two primer sets are needed for amplification of the chicken variable heavy chain (VH) and variable light chain (VL) genes. In the present study we explored the possibility to immunize chickens with antigen cocktails for the generation of recombinant antibody fragments directed to a range of human autoantigens. Two pairs of chickens were immunized with two cocktails of seven recombinant autoantigenic proteins, libraries were prepared and panned on the individual proteins. The polyclonal chicken sera reacted strongly with most of the antigens used for immunization. By creating and screening single-chain variable fragment antibody phage display libraries, recombinant monoclonal antibody fragments were isolated successfully against the autoantigens annexin XI, centromere protein B, heat shock protein B3, DNA topoisomerase I, histidyl tRNA synthetase, Ro52, Ro60, Rpp30 and U1A. In conclusion, the immunization of only four chickens with two distinct pools of a total of 14 autoantigenic proteins allowed the isolation of scFvs against nine of these antigens.