DOCSLIB.ORG

Zebrafish Plzf Transcription Factors Enhance Early Type I IFN Response

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Zebrafish Plzf Transcription Factors Enhance Early Type I IFN Response NNT : 2016SACLV016 THESE DE DOCTORAT DE L’UNIVERSITE PARIS-SACLAY PREPAREE A L’UNIVERSITE VERSAILLES SAINT-QUENTIN EN YVELINES ECOLE DOCTORALE N° 577 STRUCTURE ET DYNAMIQUE DES SYSTEMES VIVANTS SCIENCES DE LA VIE ET DE LA SANTE Par Mlle Elina Aleksejeva Défenses innées antivirales du poisson zèbre: de la signalisation aux cellules spécialisées Antiviral innate defense in zebrafish: from signalling to specialized cells Thèse présentée et soutenue à Jouy-en-Josas, le 20. Janvier, 2016: Composition du Jury : M. Herrmann, Jean-Louis PUPH INSERM, Hopital Raymond-Poincaré Président M. Lutfalla, Georges DR CNRS, Universite Montpellier 2 Rapporteur M. Nisole, Sébastien CR INSERM, Universite Paris Descartes Rapporteur Mme. Vriz, Sophie PR INSERM, CNRS, College de France Examinatrice M. Boudinot, Pierre DR INRA Jouy-en-Josas Directeur de thèse M. Levraud, Jean-Pierre DR CNRS, Institut Pasteur Co-directeur de thèse Table of contents Acknowledgements .......................................................................................................................................... 1 Preamble ........................................................................................................................................................... 2 INTRODUCTION ........................................................................................................................................... 6 CHAPTER I................................................................................................................................................... 7 Type I IFN system of mammals and fish ...................................................................................................... 7 Virus sensing and conserved signalling pathways leading to type I IFN production ............................... 8 Type I IFNs and their receptors .............................................................................................................. 13 Induction pathways of ISGs ..................................................................................................................... 15 ISG repertoire .......................................................................................................................................... 17 CHAPTER II ............................................................................................................................................... 22 PLZF transcription factor – an emerging regulator of innate responses to pathogens ................................ 22 The family of BTB/POZ transcription factors ......................................................................................... 23 Promyelocytic leukemia zinc finger (PLZF) or ZBTB16 ......................................................................... 24 PLZF protein domain-function analysis .................................................................................................. 24 Intracellular shuffling of PLZF in the context of cell cycle regulation ................................................... 26 Biological functions ................................................................................................................................. 27 PLZF involvement in anti-viral and-bacterial defence ........................................................................... 29 Fish PLZF ................................................................................................................................................ 30 CHAPTER III .............................................................................................................................................. 32 TRIM antiviral immunity in mammals and fish .......................................................................................... 32 TRIM proteins – RING-B-box-CC superfamily ....................................................................................... 33 Protein domains and their functions ....................................................................................................... 33 Intracellular localization ......................................................................................................................... 35 TRIM in antiviral innate immunty ........................................................................................................... 36 TRIMs in fish and mammals: different repertoires .................................................................................. 38 The finTRIM subset: a large fish-specific group of B30.2 TRIM proteins .............................................. 39 CHAPTER IV .............................................................................................................................................. 41 In vivo studies of leukocytes in zebrafish .................................................................................................... 41 Zebrafish immune system : general anatomy .......................................................................................... 42 Zebrafish leukocytes ................................................................................................................................ 43 RESULTS ....................................................................................................................................................... 48 Aims of the thesis and research projects ..................................................................................................... 49 CHAPTER V ............................................................................................................................................... 52 Zebrafish Plzf transcription factors augment type I IFN ............................................................................. 52 Supplementary materials ......................................................................................................................... 62 CHAPTER VI ............................................................................................................................................. 63 Steady state tissue-specific antiviral immunity: a finTRIM inducing constitutive IFN signaling is expressed at surfaces exposed to pathogens ................................................................................................ 63 Abstract.................................................................................................................................................... 65 Introduction ............................................................................................................................................. 65 Materials and methods ............................................................................................................................ 69 Results...................................................................................................................................................... 73 Discussion ................................................................................................................................................ 79 Figures ..................................................................................................................................................... 83 Supplementary materials. ........................................................................................................................ 90 References ................................................................................................................................................ 95 CHAPTER VII ............................................................................................................................................ 98 Sentinel macrophages of zebrafish neuromasts ........................................................................................... 98 Introduction ........................................................................................................................................... 100 Materials and methods .......................................................................................................................... 102 Results.................................................................................................................................................... 105 Figures ................................................................................................................................................... 111 References .............................................................................................................................................. 119 General discussion ....................................................................................................................................... 121 Zebrafish as a model to study the immune system: advantages and pitfalls ......................................... 122 Type I IFN signalling is multilayered – insights from the zebrafish model about non-canonical modulators ............................................................................................................................................. 126 Regionalization of immune response .................................................................................................... 130 Leukocytes specialized in sentinel/homeostatic functions of particular sites ........................................ 132 Conclusions ..........................................................................................................................................
Load more

Recommended publications
  • Correlation of Cytokine Level with the Severity of Severe Fever With
    Liu et al. Virology Journal (2017) 14:6 DOI 10.1186/s12985-016-0677-1 RESEARCH Open Access Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome Miao-Miao Liu1, Xiao-Ying Lei1, Hao Yu2, Jian-zhi Zhang3 and Xue-jie Yu1,4* Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. Methods: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. Results: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). Conclusion: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm.
    [Show full text]
  • Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation
    Review Primary Sjogren Syndrome: Focus on Innate Immune Cells and Inflammation Chiara Rizzo 1, Giulia Grasso 1, Giulia Maria Destro Castaniti 1, Francesco Ciccia 2 and Giuliana Guggino 1,* 1 Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Rheumatology Section, University of Palermo, Piazza delle Cliniche 2, 90110 Palermo, Italy; [email protected] (C.R.); [email protected] (G.G.); [email protected] (G.M.D.C.) 2 Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-091-6552260 Received: 30 April 2020; Accepted: 29 May 2020; Published: 3 June 2020 Abstract: Primary Sjogren Syndrome (pSS) is a complex, multifactorial rheumatic disease that mainly targets salivary and lacrimal glands, inducing epithelitis. The cause behind the autoimmunity outbreak in pSS is still elusive; however, it seems related to an aberrant reaction to exogenous triggers such as viruses, combined with individual genetic pre-disposition. For a long time, autoantibodies were considered as the hallmarks of this disease; however, more recently the complex interplay between innate and adaptive immunity as well as the consequent inflammatory process have emerged as the main mechanisms of pSS pathogenesis. The present review will focus on innate cells and on the principal mechanisms of inflammation connected. In the first part, an overview of innate cells involved in pSS pathogenesis is provided, stressing in particular the role of Innate Lymphoid Cells (ILCs). Subsequently we have highlighted the main inflammatory pathways, including intra- and extra-cellular players.
    [Show full text]
  • Interactions Between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Auto-Immune Diseases
    Type 1 interferons and the Th17 response in TB 1 http://hdl.handle.net/1765/106444 Interactions between type 1 interferons and the Th17 response in tuberculosis: Lessons learned from auto-immune diseases Bas C. Mourik1, Erik Lubberts2, Jurriaan E.M. de Steenwinkel1, Tom H.M. Ottenhoff3, Pieter J.M. Leenen4* 1Dept.Interactions of Medical Microbiology & between Infectious Diseases, Erasmus type MC, Rotterdam,1 interferons the Netherlands 2Dept.and of Rheumatology, the Th17 Erasmus MC, response Rotterdam, the Netherlands in tuberculosis: 3Dept.2 of Immunology, Erasmus MC, Rotterdam, the Netherlands Lessons learned from auto-immune 4Dept. of Infectious Diseases, LUMC, Leiden, the Netherlands Publisheddiseases in Frontiers in Immunology 2017 Apr 5;8:294. doi: 10.3389/fimmu.2017.00294. eCollection 2017 Bas C. Mourik1, Erik Lubberts2, Jurriaan E.M. de Steenwinkel1, Tom H.M. Ottenhoff3, Pieter J.M. Leenen4* 1Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, Rotterdam, the Netherlands 2Dept. of Rheumatology, Erasmus MC, Rotterdam, the Netherlands 3Dept. of Immunology, Erasmus MC, Rotterdam, the Netherlands 4Dept. of Infectious Diseases, LUMC, Leiden, the Netherlands Published in Frontiers in Immunology 2017 Apr 5;8:294. doi: 10.3389/fimmu.2017.00294. eCollection 2017 2 Erasmus Medical Center Rotterdam ABSTRACT The classical paradigm of TB immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established.
    [Show full text]
  • Interferon Type I Responses in Primary and Secondary Infections
    Immunology and Cell Biology (2008) 86, 239–245 & 2008 Australasian Society for Immunology Inc. All rights reserved 0818-9641/08 $30.00 www.nature.com/icb REVIEW Interferon type I responses in primary and secondary infections Mohammed Alsharifi, Arno Mu¨llbacher and Matthias Regner The mammalian host responds to a microbial infection with a rapid innate immune reaction that is dominated by type I interferon (IFN-I) release. Most cells of vertebrates can respond to microbial attack with IFN-I production, but the cell type responsible for most of the systemic IFN-I release is thought to be plasmacytoid dendritic cells (pDCs). Besides its anti- microbial and especially anti-viral properties IFN-I also exerts a regulatory role on many facets of the sequential adaptive immune response. One of these is being the recently described partial, systemic activation of the vast majority of B and T lymphocytes in mice, irrespective of antigen reactivity. The biological significance of this partial activation of lymphocytes is at present speculative. Secondary infections occurring within a short time span of a primary infection fail to elicit a similar lymphocyte activation response due to a refractory period in systemic IFN-I production. This period of exhaustion in IFN-I responses is associated with an increased susceptibility of the host to secondary infections. The latter correlates with well- established clinical observations of heightened susceptibility of patients to secondary microbial infections after viral episodes. Immunology and Cell Biology (2008) 86, 239–245; doi:10.1038/sj.icb.7100159; published online 8 January 2008 Keywords: type I interferon; immunoregulation; viral infections Control of viral infections by the vertebrate host involves both the fibroblast (b) and immune (g).2,3 The currently accepted classification innate and the adaptive immune response.
    [Show full text]
  • TRIM16 Antibody Cat
    TRIM16 Antibody Cat. No.: 59-182 TRIM16 Antibody Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This TRIM16 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 38-67 amino acids from the N-terminal region of human TRIM16. TESTED APPLICATIONS: WB APPLICATIONS: For WB starting dilution is: 1:1000 PREDICTED MOLECULAR 64 kDa WEIGHT: Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated October 2, 2021 1 https://www.prosci-inc.com/trim16-antibody-59-182.html PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: TRIM16 ALTERNATE NAMES: Tripartite motif-containing protein 16, Estrogen-responsive B box protein, TRIM16, EBBP ACCESSION NO.: O95361 GENE ID: 10626 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References This gene was identified as an estrogen and anti-estrogen regulated gene in epithelial cells stably expressing estrogen receptor. The protein encoded by this gene contains two B box domains and a coiled-coiled region that are characteristic of the B box zinc finger BACKGROUND: protein family. The proteins of this family have been reported to be involved in a variety of biological processes including cell growth, differentiation and pathogenesis.
    [Show full text]
  • Multiple Regulatory Regions on the 5' Side of the Mouse Ea Gene
    Proc. Nad. Acad. Sci. USA Vol. 85, pp. 3075-3079, May 1988 Immunology Multiple regulatory regions on the 5' side of the mouse Ea gene (major histocompatibility genes/y-interferon/y-interferon response region) DIMITRIS THANOS*, GEORGE MAVROTHALASSITIS*, AND JOSEPH PAPAMATHEAKIS*t *Institute of Molecular Biology and Biotechnology, Research Center of Crete, P.O. Box 1527, and tDepartment of Biology, University of Crete, 711 10 Heraklion, Crete, Greece Communicated by Fotis C. Kafatos, December 10, 1987 ABSTRACT The function of the 5'-flanking region of the motifs in the 5'-flanking region of all major histocompatibil- mouse major histocompatibility complex gene E4 has been ity complex class II genes (15, 16). We provide evidence that studied by deletion analysis with the chloramphenicol acetyl- the CS are elements necessary for the inducibility by IFN-y. transferase gene as a transient expression marker in various cell lines. This analysis reveals the presence of several control regions on the 5' side of the gene. Sequences between base pair MATERIALS AND METHODS (bp) -873 and bp -353 have a negative function in human Plasmid Constructions. The following vectors were used and mouse fibroblasts but not in the mouse macrophage line for cloning Ea and E1n gene fragments. pL51CAT was derived WEHI-3. Additional positive and negative elements have been from pSV2CAT (17) by replacing the 350-base-pair (bp) Acc mapped between bp - 353 and bp - 38. A V-interferon I-Sph I fragment by a pUC19 polylinker. pLSVOCAT was response region has been also identified within that sequence. derived from pL51CAT by elimination of the 150-bp Sma I The 5' and 3' boundaries of the -interferon response region (polylinker)-HindIII fragment.
    [Show full text]
  • Enhanced Expression of Type I Interferon and Toll-Like Receptor-3 in Primary Biliary Cirrhosis
    Laboratory Investigation (2005) 85, 908–920 & 2005 USCAP, Inc All rights reserved 0023-6837/05 $30.00 www.laboratoryinvestigation.org Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis Yasushi Takii1,3, Minoru Nakamura1,2, Masahiro Ito1,2, Terufumi Yokoyama1, Atsumasa Komori1,2, Yuki Shimizu-Yoshida1, Rumiko Nakao1, Koichiro Kusumoto1,2, Shinya Nagaoka1,2, Koji Yano1,2, Seigo Abiru1,2, Toshihito Ueki1,2, Takehiro Matsumoto1,2, Manabu Daikoku1,2, Ken Taniguchi1,2, Hikaru Fujioka1,2, Kiyoshi Migita1,2, Hiroshi Yatsuhashi1,2, Masahiro Nakashima4, Mine Harada3 and Hiromi Ishibashi1,2 1Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki, Japan; 2Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 3Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan and 4Tissue and Histopathology Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan The pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic. In order to address this issue, we analyzed by laser capture microdissection and real-time reverse transcription-polymerase chain reaction the site-specific expression of messenger RNA (mRNA) for cytokines (interferon (IFN)-a,-b,-c, interleukin (IL)-1b, -4, -6, -10, -12p40, -18, tumor necrosis factor-a) and toll-like receptors (TLRs) (TLR-2, -3, -4, -7, -9) in portal tract and liver parenchyma from patients with early-stage PBC. Expression of IFN-a,-b and TLR-3 proteins was also studied by immunohistochemistry. Autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) served as disease controls.
    [Show full text]
  • Regulation of Type I Interferons in Health and Autoimmune Disease
    Regulation of type I interferons in health and autoimmune disease Antonios Psarras Submitted in accordance with the requirements for the degree of Doctor of Philosophy (PhD) University of Leeds Leeds Institute of Rheumatic and Musculoskeletal Medicine September 2018 i Intellectual property and publication statements The candidate confirms that the work submitted is his own, except where work which has formed part of jointly-authored publications has been included. The contribution of the candidate and the other authors to this work has been explicitly indicated below. The candidate confirms that appropriate credit has been given within the thesis where reference has been made to the work of others. Chapter 1 includes data from a jointly-authored publication: Psarras A, Emery P, Vital EM. Type I interferon-mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy. Rheumatology (Oxford). 2017;56(10):1662-75. Psarras A performed the review of literature, critically appraised scientific evidences of the relevant topics and led the writing of the manuscripts. Emery revised the manuscripts for important intellectual content and final approval of the manuscript. Chapter 3 includes data from two jointly-authored publications: El-Sherbiny YM*, Psarras A*, Yusof MYM, Hensor EMA, Tooze R, Doody G, et al. A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features. Sci Rep. 2018;8(1):5793. *joint first author El-Sherbiny YM, Emery P, and Vital EM performed conception and design
    [Show full text]
  • TRIM16 Monoclonal Antibody (M02A), Clone 5G11
    TRIM16 monoclonal antibody (M02A), clone 5G11 Catalog # : H00010626-M02A 規格 : [ 200 uL ] List All Specification Application Image Product Mouse monoclonal antibody raised against a partial recombinant Western Blot (Cell lysate) Description: TRIM16. Immunogen: TRIM16 (NP_006461, 165 a.a. ~ 273 a.a) partial recombinant protein with GST tag. MW of the GST tag alone is 26 KDa. Sequence: LDAARRDKEAELQCTQLDLERKLKLNENAISRLQANQKSVLVSVSEVKAV AEMQFGELLAAVRKAQANVMLFLEEKEQAALSQANGIKAHLEYRSAEME enlarge KSKQELERMA Western Blot (Recombinant protein) Host: Mouse ELISA Reactivity: Human Isotype: IgG2a Kappa Quality Control Antibody Reactive Against Recombinant Protein. Testing: Western Blot detection against Immunogen (37.73 KDa) . Storage Buffer: In ascites fluid Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. Instruction: MSDS: Download Datasheet: Download Applications Western Blot (Cell lysate) Page 1 of 2 2020/6/25 TRIM16 monoclonal antibody (M02A), clone 5G11 Western Blot analysis of TRIM16 expression in Jurkat ( Cat # L017V1 ). Protocol Download Western Blot (Recombinant protein) Protocol Download ELISA Gene Information Entrez GeneID: 10626 GeneBank NM_006470 Accession#: Protein NP_006461 Accession#: Gene Name: TRIM16 Gene Alias: EBBP Gene tripartite motif-containing 16 Description: Omim ID: 609505 Gene Ontology: Hyperlink Gene Summary: This gene was identified as an estrogen and anti-estrogen regulated gene in epithelial cells stably expressing estrogen receptor. The protein encoded by this gene contains two B box domains and a coiled-coiled region that are characteristic of the B box zinc finger protein family. The proteins of this family have been reported to be involved in a variety of biological processes including cell growth, differentiation and pathogenesis. Expression of this gene was detected in most tissues. Its function, however, has not yet been determined.
    [Show full text]
  • Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector ORIGINAL RESEARCH published: 20 March 2017 doi: 10.3389/fimmu.2017.00285 Type I Interferon Gene Response Is Increased in Early and Established Rheumatoid Arthritis and Correlates with Autoantibody Production Julio E. Castañeda-Delgado1,2, Yadira Bastián-Hernandez1,2, Noe Macias-Segura1,3, David Santiago-Algarra1, Jose D. Castillo-Ortiz4, Ana L. Alemán-Navarro1, Pedro Martínez-Tejada5, Leonor Enciso-Moreno1, Yolanda Garcia-De Lira1, Diana Olguín-Calderón1, Leendert A. Trouw 6, Cesar Ramos-Remus7 and Jose A. Enciso-Moreno1* 1 Medical research Unit of Zacatecas, Mexican Institute of Social Security, UIMZ-IMSS, Zacatecas, Mexico, 2 National Council of Science and Technology, CONACYT, Catedras-CONACYT, Zacatecas, Mexico, 3 Departamento de fisiología y Edited by: farmacología, centro de ciencias básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Aguascalientes, Pietro Ghezzi, Mexico, 4 Unidad de Investigación en Enfermedades Crónico-Degenerativas, Guadalajara, Jalisco, México, 5 General Brighton and Sussex Medical School, Hospital: “Emilio Varela Lujan”, Mexican Institute of Social Security, IMSS, Zacatecas, Mexico, 6 Department of UK Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 7 Universidad Autonoma de Guadalajara, Jalisco, México Reviewed by: Consuelo Romero-Sanchez, Universidad El Bosque, Colombia Background: Rheumatoid arthritis (RA) is an inflammatory debilitating disease that Maria Silvia Di Genaro, National University of San Luis, affects the joints in the early and productive phases of an individual’s life. Several cyto- Argentina kines have been linked to the disease pathogenesis and are known to contribute to the Ryan Thwaites, inflammatory state characteristic of RA.
    [Show full text]
  • TREM2 R47H Exacerbates Immune Response in Alzheimer's Disease Brain
    bioRxiv preprint doi: https://doi.org/10.1101/499319; this version posted August 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. TREM2 R47H exacerbates immune response in Alzheimer’s disease brain Olena Korvatska1*, Kostantin Kiianitsa2, Alexander Ratushny3, Mark Matsushita4, Neal Beeman4, Wei-Ming Chien4, J-I Satoh5, Michael O. Dorschner6, C. Dirk Keene6, Theo K. Bammler7, Thomas D. Bird8,9, Wendy H. Raskind1,4,9,10 1 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA 2 Department of Immunology, University of Washington, Seattle, USA. 3 Seattle Biomedical Research Institute and Institute for Systems Biology, Seattle, USA. 4 Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, USA. 5 Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan. 6 Department of Pathology, University of Washington, Seattle, USA. 7 Department of Environmental and Occupational Health Sciences, Seattle, USA. 8 Department of Neurology, University of Washington, Seattle, USA. 9 Geriatric Research, Education and Clinical Center, Veteran Affairs Puget Sound Health Care System, Seattle, USA. 10 Mental Illness Research, Education and Clinical Center, Department of Veteran Affairs, Seattle, USA. *To whom correspondence should be addressed: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/499319; this version posted August 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Macrophage Activation: Dissociation of Cytotoxic Activity from Ia-A Antigen Expression (Fibroblast Interferon/Immune Interferon/Lymphokine) ELLIOTT J
    Proc. Nati. Acad. Sci. USA Vol. 80, pp. 2031-2035, April 1983 Immunology Macrophage activation: Dissociation of cytotoxic activity from Ia-A antigen expression (fibroblast interferon/immune interferon/lymphokine) ELLIOTT J. BLUMENTHAL, WALDEN K. ROBERTS, ADRIANA VASIL, AND DAVID W. TALMAGE Department of Microbiology and Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262 Contributed by David W. Talmage, December 20, 1982 ABSTRACT Peritoneal macrophages were obtained from MATERIALS AND METHODS DBA/2 mice that were untreated or after the injection of bacillus Cainette-Guerin (BCG), thioglycollate broth, proteose-peptone Mice. Our source of peritoneal macrophages was DBA/2 broth, or gamma-irradiated P-815 tumor cells. These macro- mice that were less than 3 months old (The Jackson Labo- phages were "activated" to become cytotoxic for a fibroblast cell ratory). line (L 929) by the addition of lymphokines (LKs), lipopolysac- Elicitation of Peritoneal Macrophages. Peritoneal exudate charide (LPS), or fibroblast interferon (IFN-.3), and the expres- cells were collected by lavage with 5 ml of sterile Eagle min- sion of I region-associated antigens (Ia-Ad) on the macrophages imal essential medium. Resident cells were removed from un- was examined both before and after activation. Thioglycollate- treated mice. Cells were also obtained (a) 3-4 days after the elicited macrophages became Ia-A' when activated by LKs, but injection of 1 ml of 3% thioglycollate in broth that had been they remained la-A- when activated by LPS or IFN-f3. Resident "aged" for at least 6 months at 40C or (b) 3 days after intra- macrophages and proteose-peptone-elicited macrophages re- peritoneal injection of 1 ml of 1% proteose-peptone broth.
    [Show full text]