DOCSLIB.ORG

Enhancing Haematopoeitic Stem Cell Recruitment to Injured Murine Colon

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enhancing Haematopoeitic Stem Cell Recruitment to Injured Murine Colon Enhancing Haematopoeitic Stem Cell Recruitment to Injured Murine Colon By Adrian Ian Yemm A thesis submitted to The University of Birmingham for the degree of Doctor of Philosophy College of Medical and Dental Sciences School of Clinical and Experimental Medicine University of Birmingham September 2013 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract Haematopoietic stem cells (HSCs) have been described as potential therapeutic agents for the repair of several inflammatory injuries including inflammatory bowel diseases (IBDs). However, their efficacy within clinics has been poor. This has been partially attributed to poor recruitment to sites of injury. Thus identifying the mechanisms by which HSCs are recruited to inflamed bowel, and developing strategies to enhance this recruitment, may increase their clinical efficacy. Critical adhesive mechanisms and several pre-treatment strategies to enhance adhesion to chronically (DSS induced colitis) and acutely (IR) injured murine colon were investigated in vitro and in vivo. It was found that recruitment to IR injured colon was mediated by CD49d, whereas recruitment to colitic colon was mediated by both CD18 and CD49d. In vitro investigation revealed that both hydrogen peroxide (H2O2) and platelet derived pre-treatments, such as coating HSCs with platelet microparticles (PMPs), could enhance adhesion to colon endothelial cells, immobilised endothelial counterligands ICAM-1 and VCAM-1 and frozen tissue sections. Furthermore, pre-treatment of HSCs with PMPs significantly enhanced their adhesion to chronically injured colon in vivo. These increases in adhesion were likely to be attributed to the altered distribution of integrins on the HSC surface as determined confocally. Furthermore, electron micrscopy showed that pre-treatment also resulted in overt HSC morphological changes reminiscent of activated macrophages. Overall, these investigations describe a two-component recruitment mechanism for pre-treated cells in which enhanced recruitment is dependent on both activation of stem cells and also vascular endothelium. These studies provide novel evidence that pre-treatment of HSCs can result in their increased recruitment to injured colon, a finding that may allow for stem cell therapy for IBDs to be fully realised. i Acknowledgements Publications Yemm AI, Adams DH & Kalia N. Enhancing the Recruitment of Haematopoietic Stem Cells to the injured colon in vivo. Manuscript in Preparation Kavanagh DPJ, Yemm AI, Zhao Y, Frampton J & Kalia N. (2013) Mechanisms of Adhesion and Subsequent Actions of a Haematopoietic Stem Cell Line, HPC-7, in the Injured Murine Intestinal Microcirculation in vivo. PLoS One; 8(3):e59150 Kavanagh DPJ, Yemm AI, Alexander JS, Frampton J & Kalia N. (2012) Enhancing the Adhesion of Haematopoietic Precursor Cell Integrins with Hydrogen Peroxide Increases Recruitment Within Murine Gut. Cell Transplant; 22(8): 1485-99 Oral Communications 24th UK Adhesion Society Meeting, Birmingham, 2011. Modulating haematopoietic stem cell adhesion to intestinal microvasculature Yemm AI, Adams D, Kalia N. 9th World Congress for Microcirculation, Paris, 2010. Cyto/chemokines modulate haematopoietic stem cell adhesion to endothelial cells in vitro and following murine ischaemia-reperfusion injury in vivo Yemm AI, Hamzah HH, Kavanagh DPJ, Kalia N. Poster Presentations British Microcirculation Society Meeting, Oxford, 2012. Haematopoietic stem cell adhesion to injured murine colon can be modulated by platelet microparticles and hydrogen peroxide Yemm AI, Adams D, Kalia N. Medical and Dental Sciences Research Gala, University of Birmingham 2012. Modulating haematopoietic stem cell adhesion to intestinal microvasculature with chemical and biological factors Yemm AI, Adams D, Kalia N. British Microcirculation Society Meeting, London, 2011. Modulating haematopoietic stem cell adhesion to intestinal microcirculation Yemm AI, Adams D, Kalia N. Awards University of Birmingham, College of Medical and Dental Sciences Research Gala 2012. Highly Commended Award in Poster Competition British Microcirculation Society Meeting Travel Award 2011 ii Acknowledgements Acknowledgements First and foremost, to the unending list of people who have helped, guided and, quite frankly, put up with me for the last four years a massive thank you. Without your help I would never have never made it through this, let alone (finally) put together a thesis I am proud of. To begin with I must thank Dr Neena Kalia; first you gave me a job, then taught me how to do my job, gave me a hand when the times were hard and shared a laugh when times were good. Without you I would never be in this position, so thank you for all of your time and effort, it will never be forgotten. I must also thank Professor David Adams for his help and insight over the years and his chats on his way for coffee. Similarly, to all of the members of the various stem cell groups at Birmingham, your advice and support has always been tremendous - I cannot say how much I appreciate it. I would also like to thank the Bardhan Research and Education trust for providing the funding for this work. A special mention must be made to several other people. The guys within the Kalia Lab; Kav, Becky and Joe you have been the best people I could ever hope to work with. Always willing to put up with everything, help out whenever it was needed, the enormous quantities of tea, the highly relevant and intelligent conversations (the downright weird ones too) and the welcoming laughs and smiles throughout the years, it has been an absolute pleasure to work with you all, and I miss you all already! To the guys from other labs, Hughes, Nash, Stevie T, Brenda, Giacomo and the huge list that goes on forever, thank you. Your advice and comradeship has been invaluable throughout the ordeal that is a PhD. My family must also receive the greatest of thanks. My Mam and Dad with the constant nagging and checking in on me has (mainly) been an unending help, Antony and Alison (and their families) for their advice, patience and support and to my in-laws Jo, Ian, Caz and Mike for the help, iii Acknowledgements understanding and copious amounts of alcohol! To you all thank you – I would have been bugg… I mean lost, without you all. Finally, to Heather, my fiancée and soon to be wife; I have put you through hell whilst undertaking this task and yet you have stood by me through all of it. Thank you for sharing your life with me and for being such a big part of mine – even when the majority of it has been so focussed on stem cells! I can only hope that when it is your turn to write up your thesis I can help you as much as you have helped me. I am forever grateful. iv Table of Contents Table of Contents Abstract ................................................................................................................................................. i Publications .......................................................................................................................................... ii Oral Communications ........................................................................................................................... ii Poster Presentations ............................................................................................................................ ii Awards .................................................................................................................................................. ii Acknowledgements ............................................................................................................................. iii Table of Contents ................................................................................................................................. v Table of Figures .................................................................................................................................... x Table of Tables ................................................................................................................................... xii Table of Abbreviations ...................................................................................................................... xiii Chapter 1 ................................................................................................................................................. 1 INTRODUCTION ........................................................................................................................................ 1 1.1 Inflammatory Disorders of the Colon ...................................................................................... 2 1.1.1 Inflammatory Bowel Disease........................................................................................... 2 1.1.2 Pathology of Colon Colitis Injury ..................................................................................... 3 1.1.3 Inflammatory Cells Involved in Colitis Injury ..................................................................
Load more

Recommended publications
  • C3did PNAS Pure
    Structure of the CR3 I domain in complex with C3d Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3 Goran Bajic1, Laure Yatime1, Robert B. Sim2, Thomas Vorup-Jensen3†, and Gregers R. Andersen1,† 1Dept. of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK- 8000 Aarhus, Denmark 2Dept. of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom 3Dept. of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark †Contact: Dr. Thomas Vorup-Jensen, Biophysical Immunology Laboratory, Dept. of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus, Denmark. Tel: +45 87167853; E-mail: [email protected] Dr. Gregers R. Andersen, Dept. of Molecular Biology and Genetics , Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus, Denmark. Tel: +45 87 15 55 07; E-mail: [email protected] 1 Structure of the CR3 I domain in complex with C3d Complement receptors (CR), expressed notably on myeloid and lymphoid cells, play an essential function in the elimination of complement-opsonized pathogens and apoptotic/necrotic cells. In addition, these receptors are crucial for the cross-talk between the innate and adaptive branches of the immune system. CR3 (also known as Mac-1, integrin M2, or CD11b/CD18) is expressed on all macrophages and recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. We demonstrate that the C3d moiety of iC3b harbours the binding site for the CR3 I domain, and our structure of the C3d:I domain complex rationalizes the CR3 selectivity for iC3b.
    [Show full text]
  • Characterization of Kindlin3 in Integrin Functions
    This document is downloaded from DR‑NTU (https://dr.ntu.edu.sg) Nanyang Technological University, Singapore. Characterization of kindlin3 in Integrin functions Feng, Chen 2013 Feng, C. (2013). Characterization of kindlin3 in Integrin functions. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/54828 https://doi.org/10.32657/10356/54828 Downloaded on 27 Sep 2021 23:43:18 SGT Characterization of kindlin3 in Integrin functions Feng Chen School of Biological Sciences 2013 Characterization of kindlin3 in Integrin functions Feng Chen School of Biological Sciences A thesis submitted to the Nanyang Technological University in partial fulfillment of the requirement for the degree of Doctor of Philosophy 2013 Acknowledgements First, I would like to thank my supervisor Dr. Tan Suet Mien, for his guidance during the course of my studies. He gave me many helpful suggestions for my project and has been supportive of me for trying out new ideas. I’m grateful to Dr. Yau Yin Hoe and Assoc Prof. Shochat for helping me with the SPR analyses. I wish to thank my lab mates Man Li, Yan Feng, Zhi Hong, Xiao Yan, Rhoda, Henni, Sze Wah, Manisha, Joel, Li Teng, and Jessie for their helpful suggestions and assistance. Special thanks to Dr. Tang Man Li for her guidance at the beginning of my study and Tang Xiao Yan and Ong Li Teng for the support they gave me when I encounter problems in my studies. Finally, I am indebted to my parents, husband, and friends. They provided me selfless help and encouragement during the course of my Ph.D.
    [Show full text]
  • Structural Mechanism of Laminin Recognition by Integrin
    ARTICLE https://doi.org/10.1038/s41467-021-24184-8 OPEN Structural mechanism of laminin recognition by integrin Takao Arimori 1, Naoyuki Miyazaki 1,2, Emiko Mihara 1, Mamoru Takizawa3, Yukimasa Taniguchi3, ✉ Carlos Cabañas 4,5,6, Kiyotoshi Sekiguchi3 & Junichi Takagi 1 Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained 1234567890():,; elusive. Here, we report the structures of the prototypic laminin receptor α6β1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin γ1 chain C-terminal portion pro- viding focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin β1 subunit and Asn189 of integrin α6 subunit. Laminin α5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the β-propeller domain of α6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture. 1 Laboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka, Japan. 2 Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan. 3 Division of Matrixome Research and Application, Institute for Protein Research, Osaka University, Suita, Osaka, Japan. 4 Cell-cell Communication & Inflammation Unit, Centro de Biología Molecular Severo Ochoa (CSIC- UAM), Madrid, Spain.
    [Show full text]
  • The Integrin Equilibrium: Balancing Protein-Protein and Protein-Lipid Interactions" (2012)
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2012 The Integrin Equilibrium: Balancing Protein-Protein and Protein- Lipid interactions David Thomas Moore University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biochemistry Commons, and the Biophysics Commons Recommended Citation Moore, David Thomas, "The Integrin Equilibrium: Balancing Protein-Protein and Protein-Lipid interactions" (2012). Publicly Accessible Penn Dissertations. 553. https://repository.upenn.edu/edissertations/553 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/553 For more information, please contact [email protected]. The Integrin Equilibrium: Balancing Protein-Protein and Protein-Lipid interactions Abstract On circulating platelets, the integrin fibrinogen eceptr or &alphaIIb&beta3 favors inactive conformations. Platelets rapidly activate &alphaIIb&beta3 to bind fibrinogen, mediating a platelet clot. Resting &alphaIIb&beta3 is stabilized by interactions between the &alphaIIb and &beta3 transmembrane domains. Binding of talin-1 and kindlin-3 to the integrin cytoplasmic domain stabilizes separation of the TMs and receptor activation. Src family kinases are needed for transmission of extracellular signals into the cell. We have sought to better understand how signals are transmitted across the &alphaIIb&beta3 TM domain. First we characterized the structure and dynamics of the active and inactive integrin cytoplasmic domain to determine how motifs that bind talin-1 and kindlin-3 are affected by the integrin activation state and the membrane environment. The &alphaIIb&beta3 cytoplasmic domain is disorded, while the &beta3 subunit contains two &alpha-helices, which interact with the phospholipid bilayer. The close proximity of &alphaIIb to &beta3 in the inactive state induces a kink that projects the &beta-chain parallel to the membrane surface.
    [Show full text]
  • Structural Basis of Blocking Integrin Activation and Deactivation for Anti-Inflammation Eun Jeong Park1,2*, Yoshikazu Yuki2, Hiroshi Kiyono2,3 and Motomu Shimaoka1
    Park et al. Journal of Biomedical Science (2015) 22:51 DOI 10.1186/s12929-015-0159-6 REVIEW Open Access Structural basis of blocking integrin activation and deactivation for anti-inflammation Eun Jeong Park1,2*, Yoshikazu Yuki2, Hiroshi Kiyono2,3 and Motomu Shimaoka1 Abstract Integrins mediate leukocyte accumulation to the sites of inflammation, thereby enhancing their potential as an important therapeutic target for inflammatory disorders. Integrin activation triggered by inflammatory mediators or signaling pathway is a key step to initiate leukocyte migration to inflamed tissues; however, an appropriately regulated integrin deactivation is indispensable for maintaining productive leukocyte migration. While typical integrin antagonists that block integrin activation target the initiation of leukocyte migration, a novel class of experimental compounds has been designed to block integrin deactivation, thereby perturbing the progression of cell migration. Current review discusses the mechanisms by which integrin is activated and subsequently deactivated by focusing on its structure-function relationship. Keywords: Integrin, Affinity, Activation, Deactivation, Leukocyte, Inflammation, Talin, Kindlin Introduction Integrins play a critical role in the regulation of extrava- Integrins are the largest family of cell adhesion molecules sation of leukocytes to sites of inflammation [5, 11, 12]. that mediate cell-to-cell and cell-to-matrix interactions in During rolling along the endothelial cells via selectins, leu- abroadrangeofbiologicalphenomenonsuchashost kocytes encounter chemokines expressed on endothelial defense, hemostasis, wound healing, angiogenesis, organ cells [87]. The integrin activation by chemokine enables development [3, 29, 43, 63, 73]. These functions are abrupt arrest of cells on endothelial integrin ligands. achieved via integrin bidirectional signaling across plasma Subsequently adherent leukocytes leave the initial point membrane [34, 55].
    [Show full text]
  • Exposure Arthritis Through Differential Epitope Inflammation Distinguishes Three Types of Leukocyte Membranes During Synovial CD
    The Journal of Immunology Shedding of Large Functionally Active CD11/CD18 Integrin Complexes from Leukocyte Membranes during Synovial Inflammation Distinguishes Three Types of Arthritis through Differential Epitope Exposure Louise Carstensen Gjelstrup,*,†,‡ Thomas Boesen,x Tue Wenzel Kragstrup,†,{ Annette Jørgensen,{ Nigel J. Klein,‖ Steffen Thiel,† Bent Winding Deleuran,†,{ and Thomas Vorup-Jensen*,†,‡ CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mech- anisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD18 complexes is a part of synovial inflammation in rheumatoid arthritis and spondyloarthritis but not in osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by TNF-a, which links the process to central events in the inflammatory response. The shed complexes contain multiple heterodimers of CD11/CD18, are variable in size, and differ according to the type of synovial inflammation. Furthermore, the differential structures determine the avidity of binding of the complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18 integrins is expected. Based on cell adhesion experiments in vitro, we hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1 binding sites. As reported here for synovial inflammation changes in the concentration or structure of these complexes should be considered as likely contributors to disease activity.
    [Show full text]
  • WO 2016/087245 Al 9 June 2016 (09.06.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/087245 Al 9 June 2016 (09.06.2016) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 16/24 (2006.01) A61K 39/395 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/EP2015/07733 1 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 23 November 2015 (23.1 1.2015) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 14195645.8 1 December 2014 (01. 12.2014) (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicants: DEUTSCHES KREBSFORSCHUNG- GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, SZENTRUM [DE/DE]; Stiftung des oeffentlichen Rechts, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, Im Neuenheimer Feld 280, 69120 Heidelberg (DE).
    [Show full text]
  • Structure of the Integrin Receptor Αmβ2 Headpiece in Complex with a Function-Modulating Nanobody
    bioRxiv preprint doi: https://doi.org/10.1101/2021.07.07.451531; this version posted July 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Structure of the αMβ2 headpiece in the closed conformation Structure of the integrin receptor αMβ2 headpiece in complex with a function- modulating nanobody Rasmus K. Jensen1, Henrik Pedersen1, Josefine Lorentzen1, Nick Stub Laursen2, Thomas Vorup-Jensen2, Gregers Rom Andersen1* 1 Department of Molecular Biology and Genetics, Aarhus University, Denmark 2 Department of Biomedicine, Aarhus University, Denmark *To whom correspondence should be addressed. Gregers Rom Andersen, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C DK8000 Aarhus, Denmark. [email protected] ; Tel +4530256646 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.07.07.451531; this version posted July 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Structure of the αMβ2 headpiece in the closed conformation Abstract The integrin receptor αMβ2 mediates phagocytosis of complement-opsonized objects, adhesion to the extracellular matrix and trans-endothelial migration of leukocytes. Here we present the first atomic structure of the human αMβ2 headpiece fragment in complex with the nanobody hCD11bNb1 determined at a resolution of 3.2 Å. The receptor headpiece adopts the closed conformation expected to have low ligand affinity. The crystal structure advocates that in the R77H αM variant associated with systemic lupus erythematosus, the modified allosteric coupling between ligand coupling and integrin outside-inside signalling is due to subtle conformational effects transmitted over 40 Å.
    [Show full text]
  • The Activation and Regulation of Β2 Integrins in Phagocytes And
    MINI REVIEW published: 31 March 2021 doi: 10.3389/fimmu.2021.633639 The Activation and Regulation of b2 Integrins in Phagocytes and Phagocytosis † † Hao Sun 1 , Kangkang Zhi 2 , Liang Hu 3 and Zhichao Fan 4* 1 Department of Medicine, University of California, San Diego, La Jolla, CA, United States, 2 Department of Vascular Surgery, Changzheng Hospital, Shanghai, China, 3 Department of Cardiology, Cardiovascular Institute of Zhengzhou University, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, 4 Department of Immunology, School of Medicine, UConn Health, Farmington, CT, United States Phagocytes, which include neutrophils, monocytes, macrophages, and dendritic cells, protect the body by removing foreign particles, bacteria, and dead or dying cells. Phagocytic integrins are greatly involved in the recognition of and adhesion to specific antigens on cells and pathogens during phagocytosis as well as the recruitment of Edited by: immune cells. b2 integrins, including aLb2, aMb2, aXb2, and aDb2, are the major Valentin Jaumouille´ , integrins presented on the phagocyte surface. The activation of b2 integrins is essential to Simon Fraser University, Canada the recruitment and phagocytic function of these phagocytes and is critical for the Reviewed by: fl Esther M. Lafuente, regulation of in ammation and immune defense. However, aberrant activation of b2 Complutense University of Madrid, integrins aggravates auto-immune diseases, such as psoriasis, arthritis, and multiple Spain sclerosis, and facilitates tumor metastasis, making them double-edged swords as Pontus Nordenfelt, Lund University, Sweden candidates for therapeutic intervention. Therefore, precise regulation of phagocyte Mehmet Sen, activities by targeting b2 integrins should promote their host defense functions with University of Houston, United States minimal side effects on other cells.
    [Show full text]
  • ― D12 - 1 ― 医学中央雑誌刊行会・医学用語シソーラス 第9版（ 2019） カテゴリー別リスト
    医学中央雑誌刊行会・医学用語シソーラス 第9版（ 2019） カテゴリー別リスト Amino Acids, Peptides, and Proteins D12+ Amino Acids D12-10+ Acidic Amino Acids D12-10-10+ Aspartic Acid D12-10-10-10+ # D-Aspartic Acid D12-10-10-10-10 # * Calcium Aspartate D12-10-10-10-20 # Isoaspartic Acid D12-10-10-10-30 # N-Methylaspartate D12-10-10-10-40 # * Potassium Aspartate D12-10-10-10-50 # Potassium Magnesium Aspartate D12-10-10-10-60 # Sparfosic Acid D12-10-10-10-70 # Glutamates D12-10-10-20+ # 1-Carboxyglutamic Acid D12-10-10-20-10 # * Carglumic Acid D12-10-10-20-20 # Glutamic Acid D12-10-10-20-30+ # Sodium Glutamate D12-10-10-20-30-10 # Pemetrexed D12-10-10-20-40 # Polyglutamic Acid D12-10-10-20-50+ # Paclitaxel Poliglumex D12-10-10-20-50-10 # Pyrrolidonecarboxylic Acid D12-10-10-20-60 # Alanine D12-10-20+ Alafosfalin D12-10-20-10 # Alanosine D12-10-20-20 # Alaproclate D12-10-20-30 # Beta-Alanine D12-10-20-40+ Pantothenic Acid D12-10-20-40-10+ # Hopantenic Acid D12-10-20-40-10-10 # Panthenol D12-10-20-40-10-20 # Betamipron D12-10-20-50 Brivanib Alaninate D12-10-20-60 # Lysinoalanine D12-10-20-70 # Managlinat Dialanetil D12-10-20-80 # Mimosine D12-10-20-90 # Orbofiban D12-10-20-100 # Rebamipide D12-10-20-110 # Safinamide D12-10-20-120 # Semagacestat D12-10-20-130 # Amino Acid Chloromethyl Ketones D12-10-30+ # Tosyllysine Chloromethyl Ketone D12-10-30-10 # Tosylphenylalanyl Chloromethyl Ketone D12-10-30-20 # Amino Acyl tRNA D12-10-40 # Aminobutyrates D12-10-50+ # Aminoisobutyric Acids D12-10-50-10 # Gamma-Aminobutyric Acid D12-10-50-20+ # Carpronium Chloride D12-10-50-20-10 # Gabapentin
    [Show full text]
  • Monoclonal Antibody to Cd11c Percp (100 Tests)
    PC-529-T100 Monoclonal Antibody to CD11c PerCP (100 tests) Clone: BU15 Isotype: Mouse IgG1 Specificity: The antibody BU15 reacts with CD11c (alphaX, p150), a 150 kDa integrin expressed mainly on dendritic cells and tissue macrophages. HLDA III; WS Code M 256 HLDA V; WS Code AS S143 HLDA VI; WS Code AS Ref.6 Regulatory Status: RUO Immunogen: Dendritic cells of synovial fluid Species Reactivity: Human, Monkey Preparation: The purified antibody is conjugated with Peridinin-chlorophyll-protein complex (PerCP) under optimum conditions. The conjugate is purified by size-exclusion chromatography and adjusted for direct use. No reconstitution is necessary. Storage Buffer: The reagent is provided in stabilizing phosphate buffered saline (PBS) solution containing 15mM sodium azide. Storage / Stability: Store in the dark at 2-8oC. Do not freeze. Avoid prolonged exposure to light. Do not use after expiration date stamped on vial label. Usage: The reagent is designed for Flow Cytometry analysis of human blood cells using 10 µl reagent / 100 µl of whole blood or 106 cells in a suspension. The content of a vial (1 ml) is sufficient for 100 tests. Expiration: See vial label Lot Number: See vial label Background: CD11c (p150, alphaX integrin subunit) forms complex with CD18 (beta2 integrin subunit) and is expressed mainly on tissue macrophages and dendritic cells. CD11c binds to complement fragment iC3b, fibrinogen, VCAM-1 and ICAM-2 or e.g. CD90. Like other beta2 integrins, CD11c/CD18 plays roles in cell migration and phagocytosis. Moreover, interaction of CD11c/CD18 with plasminogen regulates plasmin activities, and interaction with heparin counteracts binding of iC3b.
    [Show full text]
  • Molecular Basis for Complement Recognition by Integrin Αxβ2 Xing Chena,1, Yamei Yua, Li-Zhi Mia, Thomas Walzb, and Timothy A
    Molecular basis for complement recognition by integrin αXβ2 Xing Chena,1, Yamei Yua, Li-Zhi Mia, Thomas Walzb, and Timothy A. Springera,2 aImmune Disease Institute, Children’s Hospital Boston, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; and bHoward Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115 Contributed by Timothy A. Springer, February 6, 2012 (sent for review November 9, 2011) Integrin αXβ2 functions as complement receptor for iC3b and medi- identified and perhaps the most specifically recognized of these ates recognition and phagocytosis of pathogens. We used nega- ligands. Surface plasmon resonance studies have shown higher α β tive-stain EM to examine the X 2 interaction with iC3b. EM class affinity of a mutant, high-affinity αX I domain for iC3b than for averages of αXβ2 in complex with iC3b define the binding sites on other ligands, such as fibrinogen (17, 18). However, the molec- both the integrin and iC3b. iC3b contains C3c and thioester domain ular basis for selectivity of αXβ2 for iC3b in rosetting assays and moieties linked by a long flexible linker. The binding site is on the the binding site within iC3b have not been defined. Initially, the key ring of the C3c moiety, at the interface between the MG3 and closely related integrin αMβ2 (CR3) was reported to bind to an MG4 domains. Similar complexes are seen between αXβ2 and the C3c Arg-Gly-Asp (RGD) sequence within iC3b based on inhibition fragment. αXβ2 binds through the αX αI domain, on the face known with peptides (19).
    [Show full text]