Changes of lipopolysaccharide binding protein in serum and ascites in patients with liver cirrhosis and its clinical significance / 中国综合临床

Objective To investigate the changes of lipopolysaccharide binding protein(LBP) in serum and ascites in patients with liver cirrhosis and its clinical significance. Methods Ninety?six cases of liver cir?rhosis patients who were treated in the NO. 202 Hospital of People's Liberation Army from January 2013 to De?cember 2015 were selected as research subjects,and were divided into liver cirrhosis with spontaneous bacterial peritonitis(SBP) of 27 patients as SBP group,69 cases of patients with liver cirrhosis as non?SBP group accord?ing to the clinical diagnosis. The level of LBP in serum and ascites,routine blood test and liver function indica?tors of two groups were detected and comparative analyzed. Receiver operating curve( ROC) was drawn to select LBP diagnosis best critical value of SBP. Results The level of LBP in serum and ascites of SBP group were significantly higher than that of non?SBP group((43. 2±10. 6) μg/L vs. (19. 5±7. 5) μg/L,(280. 6±73. 9)μg/L vs. (127. 4±42. 0) μg/L),and the difference was statistically significant(t=12. 324,7. 892;P<0. 05) . ROC curve showed that the diagnosis of SBP sensitivity was 82. 30%,the specificity was 78. 36%,the area un?der ROC curve AUC value was 0. 821 when Cut?off value of LBP in ascites was 23. 5 g/L;the diagnosis of SBP sensitivity was 85. 59%,the specificity was 81. 24%,the area under ROC curve AUC value was 0. 856 when Cut?off value of LBP in serum was 152. 1μg/L. Conclusion LBP levels in serum and ascites in cirrhotic patients for the differential diagnosis of SBP has some clinical value.

Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity-related insulin resistance in adolescents / 소아과

PURPOSE: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. METHODS: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the participants was 12.9±0.3 years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (7.8±1.9 µg/mL vs. 6.0±1.6 µg/mL, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. CONCLUSION: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

Measurement of serum lipopolysaccharide binding protein for diagnosis and prognosis prediction in septic patients / 中国病理生理杂志

AIM:To investigate the role of lipopolysaccharide binding protein (LBP) for diagnosis and prog-nosis prediction in the septic patients.METHODS:A total number of 80 ICU patients were enrolled.The patients were divided into systemic inflammatory response syndrome ( SIRS) group and sepsis group, the patients in sepsis group were di-vided into non-survivor sub-group and survivor sub-group.We collected the serum samples and analyzed acute physiology and chronic health evaluation ( APACHE) II score on the first day of the patients hospitalized in ICU.In addition, we also selected 10 healthy volunteers and collected their serum samples.The serum concentrations of LBP, C-reactive protein ( CRP) and procalcitonin ( PCT) were measured by ELISA.ROC analysis of LBP, CRP, PCT and APACHE II score was conducted to discriminate among critically ill patients with sepsis and predict the prognosis of the patients with sepsis.RE-SULTS:The levels of the 4 indicators in the septic patients were higher than those in the patients of SIRS (P<0.05).In addition, serum LBP and APACHE II score in the non-survivor sub-group were higher than those in the survivor sub-group (P<0.05), whereas no difference of the PCT and CRP levels between survivors and non-survivors with sepsis was ob-served.LBP levels greater than 26.84 mg/L had 97.1% sensitivity and 95.9% specificity to discriminate between SIRS and sepsis.LBP levels greater than 54.16 mg/L had 85.2%sensitivity and 80.0%specificity for prognosis of unfavorable outcome.CONCLUSION:LBP level was more accurately correlated with diagnosis or prognosis prediction than CRP or PCT in patients with sepsis.

The diagnostic value of soluble triggering receptor expressed on myeloid cells-1 and lipopolysaccharide binding protein in neonatal serious bacterial infections / 临床儿科杂志

Objective To evaluate the accuracy of the soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and lipopolysaccharide binding protein (LBP) as diagnostic indices for neonatal serious bacterial infections (SBI). Methods A total of 171 newborns were enrolled in the study, and were classiifed into SBI group (including early-onset and late-onset), non-SBI group according to clinical manifestations, laboratory examinations and the time of disease onset. Serum sTREM-1, LBP and C-reactive protein (CRP) levels were measured. Receiver operator characteristic curve (ROC) was drawn, and the area under curve (AUC) was calculated. Each index was evaluated for the diagnostic value of neonatal SBI. Results The sTREM-1 and LBP levels were signiifcantly higher in SBI group than those in non-SBI group (P=0.000). The AUC of ROC for sTREM-1, LBP and CRP in early-onset SBI was 0.888, 0.839 and 0.706, respectively. The AUC of ROC for sTREM-1, LBP and CRP in late-onset SBI was 0.860, 0.865 and 0.705, respectively. Conclusions Both sTREM-1 and LBP are useful for the diag-nosis of neonatal SBI.

Diagnostic Role of C-reactive Protein, Procalcitonin and Lipopolysaccharide-Binding Protein in Discriminating Bacterial-Community Acquired Pneumonia from 2009 H1N1 Influenza A Infection / 결핵및호흡기질환

BACKGROUND: It is difficult but important to differentiate between bacterial and viral infections, especially for respiratory infections. Hence, there is an ongoing need for sensitive and specific markers of bacterial infections. We investigated novel biomarkers for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infections. METHODS: This was a prospective, observational study of patients with community acquired bacterial pneumonia, 2009 H1N1 Influenza A infection, and healthy controls. Serum samples were obtained on the initial visit to the hospital and stored at -80degrees C. We evaluated CRP (C-reactive protein), PCT (procalcitonin), LBP (lipopolysaccharide-binding protein) and copeptin. These analytes were all evaluated retrospectively except CRP. Receiver operating characteristic curve (ROC) analyses were performed on the resulting data. RESULTS: Enrolled patients included 27 with community acquired bacterial pneumonia, 20 with 2009 H1N1 Influenza A infection, and 26 who were healthy controls. In an ROC analysis for discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection, areas under the curve (AUCs) were 0.799 for CRP (95% Confidence interval [CI], 0.664~0.934), 0.753 for PCT (95% CI, 0.613~0.892) and 0.684 for LBP (95% CI, 0.531~0.837). Copeptin was not different among the three groups. CONCLUSION: These findings suggest that serum CRP, PCT and LBP can assist physicians in discriminating community acquired bacterial pneumonia from 2009 H1N1 influenza A infection.

LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils

Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.

LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils

Serum amyloid A (SAA) has been regarded as an important mediator of inflammatory responses. The effect of several formyl peptide receptor-like 1 (FPRL1) ligands on the production of IL-8 by SAA was investigated in human neutrophils. Among the ligands tested, LL-37 was found to specifically inhibit SAA-induced IL-8 production in transcriptional and post-transcriptional levels. Since SAA stimulated IL-8 production via ERK and p38 MAPK in human neutrophils, we tested the effect of LL-37 on SAA induction for these two MAPKs. LL-37 caused a dramatic inhibition of ERK and p38 MAPK activity, which is induced by SAA. LL-37 was also found to inhibit SAA-stimulated neutrophil chemotactic migration. Further, the LL-37-induced inhibitory effect was mediated by FPRL1. Our findings indicate that LL-37 is expected to be useful in the inhibition of SAA signaling and for the development of drugs against SAA-related inflammatory diseases.

Expression and Modulation of LL-37 in Normal Human Keratinocytes, HaCaT cells, and Inflammatory Skin Diseases

Defensins and cathelicidins (LL-37) are major antimicrobial peptides (AMPs) of the innate immune system of the human skin. In normal non-inflamed skin these peptides are negligible, but their expression can be markedly increased in inflammatory skin disease such as psoriasis. We designed this study to identify the expressions of LL-37 in normal human keratinocyte (NHK) and HaCaT cells after exposure to stimulants and to investigate difference of LL-37 expression accompanied with cell differentiation status, and come to understand difference of susceptibility to infection in atopic dermatitis and psoriasis. Expressions of LL-37 in NHKs and HaCaT cells were evaluated by using RT-PCR, Western blotting, and immunohistochemical (IHC) staining at 6, 12, and 24 hr post stimulation after exposure to Ultraviolet B irradiation and lipopolysaccharide. And expression of LL-37 in skin biopsy specimens from patients with atopic dermatitis and psoriasis was determined by immunohistochemical analysis. In time-sequential analyses of LL-37 expression revealed that LL-37 was expressed in NHKs, but not in HaCaT cells. IHC analysis confirmed the presence of abundant LL-37 in the epidermis of psoriasis. Therefore we deduced that expression of LL-37 is affected by UV irradiation, bacterial infection, and status of cell differentiation.

Change of lipopolysaccharide activity-modulating protein in serum of cirrhosis patients and its clinical significance / 中国康复理论与实践

@#ObjectiveTo explore changes of lipopolysaccharide (LPS), lipopolysaccharide-binding protein (LBP), bactericidal/permeability-increasing protein (BPI), soluble CD14 (sCD14) in blood of cirrhosis patients and their clinical significance.MethodsSerum samples of 45 cirrhosis patients were detected with chromogenic limulus amebocyte lysate assay for LPS and detected with ELISA for LBP, BPI and sCD14. While, serum samples of 15 normal subjects were used as controls.ResultsLevels of LPS, LBP, BPI and sCD14 in blood of cirrhosis patients with liver function being grade A, B and C were significantly higher than that in normal subjects. Also, those indexes fore mentioned were obviously higher in died cirrhosis patients than that in survived cirrhosis patients.Conclusion High levels of LBP, LPS and relative deficiency of BPI in cirrhosis patients accompanied with intestinal endotoxemia (IETM) may significantly increase the sensitivity of body to endotoxin.

Effects of polyclonal antibody to lipopolysaccharide binding protein on IL-10 and IL-18 mRNA expressions of alveolar macrophages in lipopolysaccharide-induced acute lung injury in rats / 第三军医大学学报

Objective To explore the effects of polyclonal antibody to lipopolysaccharide binding protein (pLBPab) on IL 10 and IL 18 mRNA expressions of alveolar macrophages in lipopolysaccharide LPS induced acute lung injury in rats. Methods A total of 40 male Wistar rats were randomly divided into 5 groups: normal control (A), LPS treated group (B), group of pLBPab preconditioning at 30 min before injection of LPS (C), group of treatment with LPS and pLBPab (D), and group of pLBPab preconditioning at 30 min after injection of LPS (E). mRNA expressions of IL 10 and IL 18 in the alveolar macrophages in each group were measured by semi quantitative reverse transcription polymerase chain reaction (RT PCR). Results The IL 10 and IL 18 mRNA expressions were highly increased respectively in the alveolar macrophage (AM?) stimulated with single LPS, but they were significantly decreased in the AM? after stimulation with LPS + pLBPab, particularly stimulation with pLBPab 30 min before LPS injection. Conclusion pLBPab can decrease the mRNA expressions such as IL 10 and IL 18 by alveolar macrophages in acute lung injury in rats induced by LPS, and LBP antibody could be used to cure some diseases such as SIRS, acute lung injury, ARDS, and septic syndrome.

Change of Lipopolysaccharide Binding Protein and Its Significance in Rats with Obstructive Jaundice / 中国普外基础与临床杂志

Objective To study the changes of lipopolysaccharide binding protein (LBP) in the serum of Wistar rats with obstructive jaundice and to investigate its potential mechanism.Methods Eighty male Wistar rats were randomly divided into obstructive jaundice group (OJ group, n =40) and sham operation group (SO group, n =40). Before operation and the 5th, 10th, 15th, 20th day after common bile duct ligation, the levels of LBP, endotoxin, tumor necrosis factor alpha (TNF ?) and interleukin 6 (IL 6) in plasma were detected in all the rats. Results LBP levels in serum increased significantly in OJ group on the 10th day after operation compared with those of SO group. Moreover, LBP levels gradually increased in OJ group with the prolongation of obstructive time. A positive correlation existed between serum LBP and plasma endotoxin, TNF ? and IL 6.Conclusion The study demonstrates that LBP in serum is high and plays an important role in the pathogenesis of multiple organ injury secondary to obstructive jaundice. It may be an appropriate way to treat patients with obstructive jaundice by decreasing LBP levels in serum.

Reconstruction,expression and characterization of dsFv V_L of human antibody to N terminal fragment of human lipopolysaccharide binding protein / 第三军医大学学报

Objective To introduce the mutated gene coding cysteine into the gene of dsFv VL of human antibody to N terminal fragment of lipopolysaccharide binding protein(LBP)and to express,purify the mutated dsFv VL in bacterium.Methods We reconstructed and sequenced the mutated gene of VL of human mAb Fab to LBP by Mega-primer PCR based on point mutagenesis method.Some codes of FWR1 of VL had been replaced by TGT in order to code cysteine.The DNA sequence of reconstructed VL was inserted into vector pET-28a(+),then VL was expressed by E.coli.BL21 star(DE3)and was purified by chromatography.Finally the activity of VL to bind NH-LBP was determined by ELISA.Results The results showed that the cysteine was introduced into the position 21 amino acid of VL to replace the threonine.The gene of VL was about 650 bp and relative molecular weight of VL was 28?103.VL could bind NH-LBP directly.Conclusion These have laid a foundation for producing the dsFv against NH-LBP.

Bioactivity of scFv antibody against human NH-lipopolysaccharide binding protein in vitro and in vivo / 第三军医大学学报

Objective To observe the bioactivity of recombinant human scFv antibody against NH-lipopolysaccharide binding protein in vitro and in vivo. Methods KM mice, weighing 20-25 g, were burnt on the back to the third degree covering 20% total body surface area. The mice in only burn group were intraperitoneally injected with 1 ?g/g LPS and those in scFv-treated group with 1 ?g/g LPS and 0.5 ?g/g scFv after burn. The mice without any treatment served as controls. All mice were sacrificed in 1, 3, 6, 12, 24 h after all treatment and the whole blood, the tissues of liver, lung and kidney were collected. The serum concentration of TNF-?, IL-6 in burnt mice with endotoxemia was detected by ELISA and the pathological changes of liver, lung and kidney tissues were observed by light microscope. The inhibition of scFv antibody of different concentrations against NH-lipopolysaccharide binding protein on FITC-LPS binding with U937 cells was assayed by FCM. Results The histopathological changes of liver, lung and kidney in mice of scFv-treated group revealed that less inflammatory cell infiltration, less degenerated cells, weaker congestion in tissue as compared with control and only burnt mice. The serum concentration of TNF-? in only burnt mice increased significantly than that of the controls (P

The associations of single nucleotide polymorphisms on bactericidal/permeability-increasing protein and lipopolysaccharide-binding protein with the susceptibility of infection / 医学研究生学报

Objective: To investigate the associations of single nucleotide polymorphisms(SNP) on bactericidal/permeability-increasing protein(BPI) and lipopolysaccharide-binding protein(LBP) with the complication of sepsis. Methods: The SNP genotypes of BPI Lys216Glu,PstⅠin intron 5,G545C,LBP Cys98Gly and Leu436Pro were examined by restriction fragment length polymorphism PCR(PCR-RFLP).Results:The rate of BPI Lys216Glu G/G genotypes and G-alleles in patients with sepsis were significantly higher than that of volunteers.The rate of BPI Lys216Glu G/G genotypes and G-alleles in nonsurviving patients were significantly higher than that of survivor patients. Conclusion: The BPI Lys216Glu G-allele may be associated with the high risk of sepsis.

CHANGES IN BLOOD LIPOPOLYSACCHARIDE, LIPOPOLYSACCHARIDE-BINDING PROTEIN、SOLUBLE CD14 LEVEL AND ITS CLINICAL SIGNIFICANCE IN PATIENTS WITH CHRONIC SEVERE VIRAL HEPATITIS B / 解放军医学杂志

To explore the changes in blood levels of lipopolysaccharide(LPS), lipopolysaccharide-binding protein(LBP),and soluble CD14 (sCD14), and their clinical significance in patients with severe chronic viral hepatitis B. blood levels of LPS were determined with chromogenic limulus amebocyte lysate assay, and LBP and sCD14 were assayed with ELISA in 24 patients of severe chronic viral hepatitis B. 10 normal subjects and 16 patients with chronic hepatitis B were also enrolled as controls. The results showed that the blood levels of LPS, LBP and sCD14 were significantly higher in patients with the early stage, midterm, late periods of severe chronic viral hepatitis B than in normal subjects and in those with chronic hepatitis B. The blood levels of LPS, LBP and sCD14 were also significantly higher in patients who died of severe chronic viral hepatitis B than in survivors of the same disease. It suggested that when patients with severe chronic viral hepatitis B were complicated by intestinal endotoxemia (IETM), the sensitivity of Kupffer cells to endotoxin was significantly increased, resulting in hepatocyte injury by TNF ?,even in the presence of very low endotoxin concentration .

Lipopolysaccharide-binding protein inhibitory peptide inhibits the binding of LPS to U937 cells / 中国病理生理杂志

AIM:To investigate the inhibitory effect of P12,a kind of lipopolysaccharide(LPS)-binding protein(LBP) inhibitory peptide,on the binding of LPS to macrophage in vitro.METHODS:Human monocyte-like cell line(U937 cells) was grown in RPMI-1640 and stimulated with PMA in order to induce their differentiation to macrophage stage.The relative affinity of P12 to LPS was determined by enzyme-linked immunosorbent assay(ELISA).The effects of P12 on the binding of LPS to U937 cells were determined by flow cytometry analysis.The production of tumor necrosis factor-alpha(TNF-?) was measured by ELISA.RESULTS:The relative binding activity of P12 to LPS was higher than that of LBP in the same mass concentration.P12 inhibited the binding of FITC-conjugated LPS(FITC-LPS) to U937 cells.The productions of TNF-? was also significantly suppressed by P12.CONCLUSION:The results suggest that blockage of LBP at the inflammatory sites might attenuate LPS-induced circulatory shock.

Influence of glycine on LBP mRNA expression induced by LPS in the liver of rats / 中国病理生理杂志

AIM: To study the influence of glycine(GLY) on lipopolysaccharide-binding protein(LBP) mRNA expression induced by LPS. METHODS: The level of LBP mRNA expression in liver tissues of rats was examined by RT-PCR,and the effects of glycine on LBP mRNA expression in liver tissues of rats induced by LPS were investigated. RESULTS: The level of LBP mRNA expression in hepatic tissue of rats in the LPS group was significantly higher than that in the control group( P

Effects of lipopolysaccharide binding protein on activation of p38 signaling pathway induced by LPS in macrophages / 中国病理生理杂志

AIM: To investigate the regulatory effects of lipopolysaccharide binding protein(LBP)on activation of p38 signaling pathway induced by lipopolysaccharide(LPS)in alveolar macrophages. METHODS: The LBP from actue phase rat serum was purified by ammonium sulphate precipitation, Bio-Rex70 resin and the MonoQ column. Rat alveolar macrophages were exposed to LPS (0 01 mg/L or 1 mg/L) the various concentrations of LBP(0 mg/L, 0 01 mg/L, 0 1 mg/L,1 mg/L and 10 mg/L) Western blotting were used to detect phospho-p38 in alveolar macrophages RESULTS: SDS-PAGE analysis indicated that the purified preparation of rat LBP showed homogeneity and the molecular weight was 60 kD.The binding of lipopolysaccharide to mononuclear cells were enhanced by purified rat LBP. Stimulation of rat alveolar macrophages with LPS at concentration of 0.01 mg/L was LBP dependent. LBP at concentrations up to 1 mg/L was able to increase the activation of p38. However , when LBP concentrations were further increased to 10 mg/L, the phosphorylation levers of p38 were lower as compared with that in the presence of 1 mg/L. Stimulation of rat alveolar macrophages with LPS at concentrations of 1 mg/L was LBP-independent. CONCLUSION: The activation of p38 induced by LPS at lower concentration(0.01 mg/L ) was LBP-dependent, meanwhile, LPS at higher concentration (1 mg/L ) was LBP-independent.

Protective Mechanism of Recombinant Bactericidal Permeability-increasing Protein 21 in Rat Endotoxemia / 中华医院感染学杂志

OBJECTIVE To investigate the protective mechanism of recombinant bactericidal permeability-increasing protein 21(rBPI21) in rat endotoxemia.METHODS The different dosage of rBPI21 in endotoxemia rats was injected and the changes in lipopolysaccharide(LPS), lipopolysaccharide binding protein(LBP) and tumor necrosis factor ?(TNF?) contents in blood of different group rats were continuously observed.RESULTS At 6 and 12 hours,the levels of LPS in rBPI21 treatment 1 group(rBPI21 dosage 0.625 mg/kg) were significantly lower than those in endotoxin group at the same time.Serum LBP and TNF? in rBPI21 treatment 1 group were both lower than those in endotoxin group at any time point.Compared with the endotoxin group,the levels of LPS,LBP,and TNF? in rBPI21 treatment 2,3 and 4 groups(rBPI21 dosage 1.25 mg/kg,2.5mg/kg,and 5.0mg/kg,respectively) markedly dropped at any time points,the survival rates were increased from 16.7%(endotoxin group) to 58.3%,91.7% and 100%(rBPI21 treatment 2,3,and 4 groups) individually.CONCLUSIONS The protection of rBPI21 in endotoxemia rats is primarily achieved through neutralizing LPS,decreasing LPS activity in vivo and inhibiting LBP and TNF-? synthesis.

Changes of Hematoxin,Lipopolysaccharide,Lipopolysaccharide Binding Protein/Membrane CD_(14) in Children with Systemic Inflammatory Response Syndrome / 实用儿科临床杂志

Objective To investigate the effect of hematoxin,lipopolysaccharide(LPS),lipopolysaccharide binding protein(LBP)/membrane CD14(mCD14) in occurrence and development of systemic inflammatory response syndrome(SIRS) in children.Methods Serum LPS,LBP,mean fluorescence intensity(MFI) of mCD14 on monocytes of 30 patients with SIRS were measured,at the same time 21 healthy children had been chosen to serve as control group.Results Compared with control group,the serum LPS,LBP,MFI of mCD14 on monocytes of patients with SIRS were significantly higher(Pa