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Study of the effect of atorvastatin on the interaction between ICAM-1 and CD11b by live-cell single-molecule force spectroscopy

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Science China Chemistry 2010年第4期53卷 752-758页

作者： LI Yi1, SHI XiaoLi2, LIU HuiLiang1, YI ShaoQiong3, ZHANG XueJie2 & FANG XiaoHong2 1Department of Cardiology, the General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China 2Beijing National laboratory for Molecular Sciences Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China 3state key laboratory of pathogen and biosecurity Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China 1. Department of Cardiology the General Hospital of Chinese People’s Armed Police Forces Beijing 100039 China2. Beijing National Laboratory for Molecular Sciences Chinese Academy of Sciences Beijing 100190 China4. Institute of Chemistry Chinese Academy of Sciences Beijing 100190 China3. State Key Laboratory of Pathogen and Biosecurity Beijing 100071 China5. Beijing Institute of Microbiology and Epidemiology Beijing 100071 China

The interaction between the cell adhesion molecule CD11b and its ligand ICAM-1 plays an important role in inflammatory responses in the disease of atherosclerosis. Atorvastatin is a commonly prescribed statin drug which has been considered as one of the most potent therapeutic agents for atherosclerosis due to its lipid-lowering effect. Recently, there is a growing body of evidence that atorvastatin has anti-inflammatory effect. We have applied the advanced method of live-cell single-molecule force spectroscopy to investigate the effect of atorvastatin on adhesion force between ICAM-1 and CD11b. Our result showed that single-molecule binding force of ICAM-1 and CD11b detected by AFM in the living cells was about 40 pN, and atorvastatin did not affect this force by blocking ICAM-1 or CD11b. This was different from the ICAM-1 monoclonal antibody, which could directly reduce the binding force of ICAM-1 and CD11b. Flow cytometry results revealed that atorvastatin pretreatment decreased the ICAM-1 expression in TNF-α activated HUVECs, which may contribute to its anti-inflammatory effect. The study provides a new approach to study anti-inflammatory mechanism for clinic drugs.

关键词： atherosclerosis atorvastatin atomic force microscopy single-molecule force spectroscopy protein-protein interaction

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Immunological dynamics in response to two anthrax vaccines in mice

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Science China(Life Sciences) 2008年第10期51卷 872-878页

作者： Lü Jin, HE Rui, DONG Mei, ZHANG LiangYan & WANG XiLiang state key laboratory of pathogen and biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China 1. state key laboratory of pathogen and biosecurity Beijing Institute of Microbiology and Epidemiology Beijing 100071 China

In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu- nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac- cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza- tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex- periment when the plasma cell responses in the AVA group were reduced to a very low level. The re- sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re- sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy. These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for vacci

关键词： anthrax vaccine adsorbed live spore vaccine antigen secreting cells immunological response ELISPOT

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Genomic research for important pathogenic bacteria in China

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Science China(Life Sciences) 2009年第1期52卷 50-63页

作者： YANG RuiFu1,GUO XiaoKui2,YANG Jian3,JIANG YongQiang1,PANG Bo4,CHEN Chen5,YAO YuFeng2,QIN JinHong2 & LI QingTian2 1 laboratory of Analytical Microbiology,state key laboratory of pathogen and biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China 2 Department of Medical Microbiology and Parasitology,Institutes of Medical Sciences,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China 3 state key laboratory for Molecular Virology and Genetic engineering,Institute of pathogen Biology,Chinese Academy of Medical Sciences,Beijing 100176,China 4 state key laboratory for Infectious Disease Prevention and Control,Institute for Communicable Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China 5 Beijing Genomics Institute at Shenzhen,Shenzhen 518083,China 1. laboratory of Analytical Microbiology State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing 100071 China 2. Department of Medical Microbiology and Parasitology Institutes of Medical Sciences Shanghai Jiao Tong University School of Medicine Shanghai 200025 China 3. state key laboratory for Molecular Virology and Genetic engineering Institute of Pathogen Biology Chinese Academy of Medical Sciences Beijing 100176 China 4. state key laboratory for Infectious Disease Prevention and Control Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing 102206 China 5. Beijing Genomics Institute at Shenzhen Shenzhen 518083 China

Rapid accumulation of bacterial genomic data offered an unprecedented opportunity to understand bacterial biology from a holistic view of *** can thus closely look at the way in which a pathogen is evolved,and these data has been applied to molecular epidemiology and microbial forensics,and screening of novel diagnostic,vaccine and drug *** newly developed high-throughput low-cost sequencing technologies,such as 454,Solexa and SOLiD,will promote the acquisition and application of genomic data in new research areas that we dared not imagine previously,such as the metagenomics of human gastric-intestinal tract,for better and comprehensive understanding of human health and disease.

关键词： genome pathogenic bacteria sequencing application

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Research progress in Shigella in the postgenomic era

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Science China(Life Sciences) 2010年第11期53卷 1284-1290页

作者： PENG JunPing, YANG Jian & JIN Qi state key laboratory for Molecular Virology and Genetic Engineering, Institute of pathogen Biology,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China 1. state key laboratory for Molecular Virology and Genetic Engineering Institute of Pathogen Biology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100176 China

Gram-negative,facultative intracellular anaerobes of the genus Shigella,the principal etiologic agents of shigellosis,continue to pose a threat to public health. Shigellosis causes 1.1 million deaths with over 164 million annual cases. The Shigella spp. can be divided into four serogroups:Shigella dysenteriae,Shigella flexneri, Shigella boydii and Shigella sonnei. The completion of seven Shigella genome sequences of representative strains from each of the Shigella species has introduced an era of whole-genome *** paper reviews contemporary understanding of genomics,transcriptomics,proteomics and the structural biology of Shigella.

关键词： Shigella genomics transcriptomics proteomics structural biology

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Neutralization and enhancement of enterovirus type 71 infection by human IgG subclasses

Neutralization and enhancement of enterovirus type 71 infect...

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2012全国临床微生物与感染免疫学术研讨会

作者： Qin Chengfeng,Cao Ruiyuan,DongDayong,Han Jianfeng,Chen Wei,Qin Ede state key laboratory of pathogen and biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China.

Objective Human enterovius 71(EV71) has emerged as the leading cause of viral encephalits in young children in Asia-Pacific *** antiviral drugs or vaccines is currenlty *** antibibies confers protection against EV71 infection in animial and clinical studies,while sub-neutalizing concentrations of antibody were rencently demonstrated to augment the infectivity of EV71 via a mechanism termed antibody-dependent enhancement (ADE).Human IgG antibodies include four subclasses and each subclass serves somewhat different ***,the association of human IgG subclass with EV71 infection has not been investigated. Methods Commercial human intravenous immunoglobulin(IVIG) preparations manufactured from Chinese plasma donors were subjected to fractionation by pH gradient elution with a protein A-conjugated affinity column. Each IgG subclass fraction was then subjected to in vitro neutralization tests in human rhabdomyosarcoma RD cells and ADE assays in human monocytic THP-1 cells according to the standard protocol. Results Each IgG subclass was sucessfully fractionated,and slight variation of subclass distribution was observed among different lots of IVIG *** assays against EV71 showed that the neutralizing titer of IgGl subclass was significantly higher than that of IgG2,while IgG3 had no neutralization *** majority of the neutralizing capacity of IVIG was due to IgGl subclass,and IgG2 only played a minor role(Fig.1). Significantly,ADE assays showed IgGl and IgG3 subclasses exhibited peaked ADE activities at concentrations of 2.0μg/ml and 0.2μg/ml,respectively,but few ADE potential was observed for ***,each IgG subclass plays distinct roles in controlling EV71 infection. Conclusions We for the first characterize and clarify the distinct function of each IgG subclass against EV71 *** finding helps understand the pathogenesis of EV71 infection,and is of critical importance for the rational desig

关键词： Enterovirus type 71 Neutralization Antibody dependent enhancement Human IgG subclasses Vaccine

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Risk analysis for the highly pathogenic avian influenza in China's mainland using meta-modeling

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Science Bulletin 2010年第36期 4169-4179页

作者： CAO ChunXiang1, XU Min1,3, CHANG ChaoYi1,3, XUE Yong1, ZHONG ShaoBo1, FANG LiQun2, CAO WuChun2, ZHANG Hao1, GAO MengXu1,3, HE QiSheng1,3, ZHAO Jian1,3, CHEN Wei1,3, ZHENG Sheng1,3 & LI XiaoWen1 1 state key laboratory of Remote Sensing Science, the Institute of Remote Sensing Applications of the Chinese Academy of Sciences, Beijing 100101, China 2 Beijing Institute of Microbiology and Epidemiology, state key laboratory of pathogen and biosecurity, Beijing 100071, China 3 Graduate University of the Chinese Academy of Sciences, Beijing 100049, China

A logistic model was employed to correlate the outbreak of highly pathogenic avian influenza (HPAI) with related environmental factors and the migration of birds. Based on MODIS data of the normalized difference vegetation index, environmental factors were considered in generating a probability map with the aid of logistic regression. A Bayesian maximum entropy model was employed to explore the spatial and temporal correlations of HPAI incidence. The results show that proximity to water bodies and national highways was statistically relevant to the occurrence of HPAI. Migratory birds, mainly waterfowl, were important infection sources in HPAI transmission. In addition, the HPAI outbreaks had high spatiotemporal autocorrelation. This epidemic spatial range fluctuated 45 km owing to different distribution patterns of cities and water bodies. Furthermore, two outbreaks were likely to occur with a period of 22 d. The potential risk of occurrence of HPAI in China's mainland for the period from January 23 to February 17, 2004 was simulated based on these findings, providing a useful meta-model framework for the application of environmental factors in the prediction of HPAI risk.

关键词： highly pathogenic avian influenza meta-modeling remote sensing geographical information system Bayesian maximum entropy logistic regression spatiotemporal autocorrelation

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Development of colloidal gold-based immunochromatographic assay for the rapid detection of ricin toxin

Development of colloidal gold-based immunochromatographic as...

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第九届中国生物毒素学术研讨会

作者： Jing-Hong WANG,Lin KANG,Shan GAO,Chong NIE,Jing-Lin WANG laboratory of Toxinology,The state key laboratory of pathogen and biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,Beijing 100071, China

＜正＞A rapid,signal step and highly sensitive immunochromatographic（IC） assay was developed to detect *** assay was based on the sandwich format using monoclonal antibody（Mab） and polyclonal antibody（Pab） of two distinct *** anti-ricin A chain Mab was immobilized as a capture antibody on a porous nitrocellulose membrane where goat anti-rabbit IgG（control line） was separately coated with,while the other anti-ricin B chain Pab was conjugated to colloidal gold particles that served as a detector *** ricin-containing sample was added to the membrane and allowed to react with Pab-coated *** mixture was then passed along the porous membrane by capillary action past the Mab in the detection zone,which will bind the particles that had ricin bound to their surfaces,giving a red color within this detection zone with an intensity proportional to ricin *** the absence of ricin,no immunogold was bound to the solid-phase antibody. With this method,50ng/mL of ricin was detected in less than 10 min,and the assay also showed no cross reaction to ricin toxin.

关键词： Colloidal gold Immunochromatographic assay Ricin Antibody

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Molecular characterization of the Mg2+-responsive PhoP regulator in control of the intracellular growth of Yersinia pestis

Molecular characterization of the Mg2+-responsive PhoP regul...

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首届全国微生物基因组学学术研讨会

作者： Dongsheng Zhou, Long Qin, Yingli Li, He Gao, Yu Wang, Yajun Song, and Ruifu Yang state key laboratory of pathogen and biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China

Yersinia pestis is considered as a facultative intracellular pathogen capable of surviving and growing within macrophages. The Mg2+-responsive PhoP regulator was previously shown to be important for Y. pestis survival in macrophage and under macrophage-induced stresses of low pH, oxidative stress, high osmolarity and antimicrobial peptides. In this work, a phoP mutan of Y. pestis is generated using the Red cloning procedure. Microarray transcriptional profiling of the phoP mutant in response to low Mg2+ stimulus reveals at least 706 genes whose expression is dependent on PhoP, representing approximately 16% of the total protein-coding capacity of the Y. pestis genome. The microarray data provides a framework of candidate PhoP targets for further biochemical investigation. A total of 45 putative operons are subsequently shown to be under the direct control of PhoP by using electrophoretic

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基于荧光检测的新型细胞传感器

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生物化学与生物物理进展 2011年第2期38卷 185-190页

作者：辛文文王景林军事医学科学院微生物流行病研究所病原微生物生物安全国家重点实验室北京100071

主要介绍了一类基于荧光检测的新型细胞传感器,这类传感器利用免疫细胞表面分子特异性识别、结合抗原的特性和生物(或化学)发光技术,通过检测荧光信号在数分钟内达到检测病原体或其他抗原的目的.这类传感器的发光原理主要是利用钙离子... 详细信息

主要介绍了一类基于荧光检测的新型细胞传感器,这类传感器利用免疫细胞表面分子特异性识别、结合抗原的特性和生物(或化学)发光技术,通过检测荧光信号在数分钟内达到检测病原体或其他抗原的目的.这类传感器的发光原理主要是利用钙离子敏感型化学荧光探针发光,如Fluo-4等,或钙离子敏感型发光蛋白发光,如水母发光蛋白、绿色荧光蛋白等.现在已经应用的主要是B细胞传感器和肥大细胞传感器.这类传感器具有灵敏度高、检测准确、反应速度快的优点.同时又存在交叉反应、细胞不易保存等不足之处.这类传感器在疾病诊断、环境监测、生物战剂检测等领域具有较大的应用前景.

关键词：细胞传感器荧光检测免疫细胞病原体检测

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Comparative transcriptomics analysis of environmental modulation of gene expression in Yersinia pestis

Comparative transcriptomics analysis of environmental modula...

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首届全国微生物基因组学学术研讨会

作者： Yanping Han, Dongsheng Zhou, Jingfu Qiu, Long Qin, Yajun Song, Jin wang, Zhaobiao Guo, Ruifu Yang state key laboratory of pathogen and biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China

Yersinia pestis, the etiological agent of plague, alternatively growing in the flea or in warm-blood mammalian hosts, is a facultatively intracellular bacterium. To survive the broad range of stressful environments, Y. pestis must make appropriate adaptive responses, primarily reflected by the transcriptional changes of specific sets of genes. In our lab we have examined the genome-wide transcriptional profilings of Y. pestis upon exposure to a variety of environmental stresses, such as temperature alteration, high salinity/osmolarity, hydrogen peroxide, low magnesium ion, iron deprivation, minimal medium and treatment of antibiotics and antibacterial peptides. It was noticed that the transcriptional regulation upon multiple stresses was characteristic of the well-known virulence genes. Submitting all the transcriptome data of Y. pestis available for computational clustering, certain larger groups of clustered genes were found. Further examination showed that those genes in the same cluster had a strong tendency to be assigned to related categories or share common roles in a wide variety of cellular functions of Y. pestis. Of all the co-regulated genes by multiple stresses in Y. pestis, one hundred and eighty eight genes were predicted to belong to forty-five potential operons on the basis of existing knowledge about transcriptional changes, intergenic region and genomic annotation. In addition, the metabolic pathway of some clustered gene was mapped based on genomic information, gene expression data and KEGG pathway information. Pattern discovery showed that a conservative motif was present in the promoter regions of a large group of clustered genes including many genes known as iron/heme uptake and ultilization. Finally, those genes regulated specific to a certain condition were also identified in Y. pestis, raising the possibility of a better understanding of the processes involved.

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