DOCSLIB.ORG

Downloaded From

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Downloaded From Kruppel-Like Factor 4 Is Essential for Inflammatory Monocyte Differentiation In Vivo This information is current as Jonathan K. Alder, Robert W. Georgantas III, Richard L. of September 24, 2021. Hildreth, Ian M. Kaplan, Sebastien Morisot, Xiaobing Yu, Michael McDevitt and Curt I. Civin J Immunol 2008; 180:5645-5652; ; doi: 10.4049/jimmunol.180.8.5645 http://www.jimmunol.org/content/180/8/5645 Downloaded from References This article cites 48 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/180/8/5645.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Kruppel-Like Factor 4 Is Essential for Inflammatory Monocyte Differentiation In Vivo1 Jonathan K. Alder,* Robert W. Georgantas III,* Richard L. Hildreth,* Ian M. Kaplan,* Sebastien Morisot,* Xiaobing Yu,*‡ Michael McDevitt,§ and Curt I. Civin2*† Several members of the Kruppel-like factor (KLF) family of transcription factors play important roles in differentiation, survival, and trafficking of blood and immune cell types. We demonstrate in this study that hematopoietic cells from KLF4؊/؊ fetal livers (FL) contained normal numbers of functional hematopoietic progenitor cells, were radioprotective, and performed as well as KLF4؉/؉ cells in competitive repopulation assays. However, hematopoietic “KLF4؊/؊ chimeras” generated by transplantation of (KLF4؊/؊ fetal livers cells into lethally irradiated wild-type mice completely lacked circulating inflammatory (CD115؉Gr1؉ monocytes, and had reduced numbers of resident (CD115؉Gr1؊) monocytes. Although the numbers and function of peritoneal ؊ ؊ ؊ ؊ macrophages were normal in KLF4 / chimeras, bone marrow monocytic cells from KLF4 / chimeras expressed lower levels Downloaded from of key trafficking molecules and were more apoptotic. Thus, our in vivo loss-of-function studies demonstrate that KLF4, previously shown to mediate proinflammatory signaling in human macrophages in vitro, is essential for differentiation of mouse inflammatory monocytes, and is involved in the differentiation of resident monocytes. In addition, inducible expression of KLF4 in the HL60 human acute myeloid leukemia cell line stimulated monocytic differentiation and enhanced 12-O-tetradecanoylphorbol 13-acetate induced macrophage differentiation, but blocked all-trans-retinoic acid induced granulocytic differentiation of HL60 cells. The inflammation-selective effects of loss-of-KLF4 and the gain-of-KLF4-induced monocytic differentiation in HL60 cells identify http://www.jimmunol.org/ KLF4 as a key regulator of monocytic differentiation and a potential target for translational immune modulation. The Journal of Immunology, 2008, 180: 5645–5652. lthough members of the Sp/Kruppel-like factor proinflammatory signaling in human macrophages (17). KLF4 (KLF)3 family of transcription factors, KLF1–17 and expression is induced in response to IFN-␥, LPS, or TNF-␣ in A Sp1–8 in mammals, share a high degree of sequence human macrophages, and decreases in response to TGF-␤1. homology in their zinc-finger regions, their non-DNA binding KLF4 binds to and induces the iNos promoter, and KLF4 portions are diverse in composition and function (1–4). Several ␥ knockdown diminishes LPS or IFN- induction of iNOS. Re- by guest on September 24, 2021 of the 17 mammalian KLFs, including KLF1, KLF2, KLF3, cently, Feinberg et al. demonstrated that KLF4 is highly ex- KLF6, KLF11, and KLF13, have been shown to play crucial pressed in the human monocyte/macrophage lineage and ec- roles in hematopoiesis and immunity (5–13). In addition to reg- topic expression of KLF4 induces monocytic differentiation of ulating quiescence in T lymphocytes, KLF2 (LKLF; KLF4’s HL60 cells (18). KLF4 was demonstrated to be a downstream closest family member) regulates trafficking of T lymphocytes target of the Ets transcription factor PU.1 and a direct transcrip- by regulating the expression of key trafficking molecules, in- tional regulator of CD14. The authors also showed that common ␤ cluding L-Selectin (CD62L) and 7 integrin (3, 4, 14). KLF4 myeloid progenitors and hematopoietic stem-progenitor cells (also known as gut KLF (15)) itself down-modulates expression (HSPCs) from KLF4Ϫ/Ϫ mice produced fewer monocytic cells of the CD11d myeloid-associated molecule (16) and mediates and increased granulocytic cells in clonogenic assays (18). Al- though these studies strongly implicate KLF4 as a regulator of *Divisions of Immunology and Hematopoiesis, †Pediatric Oncology, Sidney Kimmel macrophage differentiation and activation, detailed in vivo stud- Comprehensive Cancer Center, ‡Stem Cell Program, Institute of Cell Engineering, ies have been difficult due to nonhematopoietic lethality of § and Hematology Division, Department of Medicine, Johns Hopkins University Ϫ/Ϫ School of Medicine, Baltimore, Maryland complete KLF4 deficiency (KLF4 ) shortly after birth (19). Monocytes are the circulating precursors of tissue macrophages Received for publication July 11, 2007. Accepted for publication February 12, 2008. and dendritic cells. Monocyte-macrophage development in the mouse The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance is thought to occur in ordered progression, starting from a with 18 U.S.C. Section 1734 solely to indicate this fact. CD115ϩLy6CϩCCR2ϩ precursor in the bone marrow (BM), which 1 This research was supported in part by a Fellow Award from the National Foun- gives rise to three distinct subpopulations of circulating blood dation for Cancer Research and National Institutes of Health Grant CA070970. monocytes: 1) Ly6ChighCD62LϩCCR2ϩ“inflammatory” monocytes, 2 Address correspondence and reprint requests to Dr. Curt I. Civin, BB CRB 1 which are short-lived and migrate to sites of inflammation; 2) Room 2M44, 1650 Orleans Street, Baltimore, MD 21231. E-mail address: low Ϫ Ϫ [email protected] Ly6C CD62L CCR2 “resident” monocytes, which remain in the high 3 Abbreviations used in this paper: KLF, Kruppel-like factor; HSPC, hematopoietic circulation longer than their Ly6C counterparts and are thought to stem-progenitor cell; BM, bone marrow; ES, embryonic stem; HSC, hemopoietic generate and replace resident dendritic cells and macrophages; and 3) stem cell; HPC, hematopoietic progenitor; FL, fetal liver; wt, wild type; PE, perito- a small population of Ly6Cmid cells, which may represent either a neal exudate; TPA, 12-O-tetradecanoylphorbol 13-acetate; RA, retinoic acid; ER, estrogen receptor; 4HT, 4-hydroxy-tamoxifen; CFC, colony-forming cell; SCF, functionally distinct population of monocytes or simply the transition stem cell factor; M-CSF, monocyte-CSF; PI, propidium iodide; qRT-PCR, from Ly6Chigh to Ly6Clow. All three monocyte subpopulations quantitative-RT-PCR. have the ability to differentiate into macrophages or dendritic Copyright © 2008 by The American Association of Immunologists, Inc. 0022-1767/08/$2.00 cells in vitro (20). www.jimmunol.org 5646 INFLAMMATORY MONOCYTE DIFFERENTIATION REQUIRES KLF4 KLF4 is expressed at high levels in mouse and human embry- press a KLF4-estrogen receptor (ER) fusion and GFP (see below) were ϩ onic stem (ES) cells; and recently, expression of KLF4, along with enriched by FACS-sorting for GFP cells, followed by limiting dilution three other transcription factors (Oct3/4, Sox2, and c-Myc), was cloning. At least three clones were examined for each construct. In brief, 4-hydroxy-tamoxifen (4HT; in 100% ethanol) was added to cell cultures to found to be sufficient to induce developmental reprogramming of achieve a final concentration of 200 nM. TPA and all-trans-RA were pur- mature mouse fibroblasts to reacquire key properties of pluripotent chased from Sigma-Aldrich and resuspended in DMSO or ethanol, respec- ES cells (21–25). KLF4 mediates the binding of Oct3/4 and Sox2 tively. For hematopoietic colony-forming cell (CFC) assays, 5 ϫ 104 to the mouse Lefty1 proximal promoter (26). To date, however, mouse FL or BM cells were plated in methylcellulose medium (Stem Cell Technologies) supplemented with 50 ng/ml recombinant mouse stem cell Lefty1 is the only known ES-specific KLF4 target, and the mech- factor (SCF), 10 ng/ml recombinant mouse IL-3, 10 ng/ml recombinant anism by which KLF4 participates in reprogramming of mouse human IL-6, and 3 U/ml recombinant human erythropoietin (all cytokines fibroblasts remains cryptic. from PeproTech). Monocyte-macrophage-specific CFC assays were per- We previously identified KLF4 among transcripts over-ex- formed as above, except medium was supplemented only with 50 ng/ml pressed in human hemopoietic stem cell (HSC)-enriched popula- SCF
Load more

Recommended publications
  • Pearls of Laboratory Medicine Transcript Document
    Pearls of Laboratory Medicine www.traineecouncil.org TITLE: Transfusion Support in Hematopoietic Stem Cell Transplant PRESENTER: Erin K. Meyer, DO, MPH Slide 1: Title Slide Hello, my name is Erin Meyer. I am the medical director of apheresis and associate medical director of Transfusion Services at Nationwide Children’s Hospital in Columbus Ohio. Welcome to this Pearl of Laboratory Medicine on “Transfusion Support in Hematopoietic Stem Cell Transplant or HSCT.” Slide 2: Transfusion Support for Hematopoietic Stem Cell Transplant (HSCT) The objectives of my talk are a brief overview of the different types of HSCT followed by a review of the sources of HSCT available and transfusion thresholds for patients receiving the different types of HSCT. Finally, I will discuss ABO-incompatible HSCT with a focus on the complications of and transfusion support for each possible ABO-incompatible combination. Hematopoietic stem cells came to light after the dropping of the atomic bombs in 1945. People who survived the initial explosions later died of bone marrow failure from radiation. A series of sentinel experiments by Till and McCulloch in the 1960s then showed that transfer of bone marrow cells from donor mice into lethally irradiated recipient mice resulted in the formation of colonies of myeloid, erythroid, and megakaryocytic cells in the recipient’s spleen approximately 7-14 days later. Stem cells have two very unique properties: the ability to self-renew and the ability to regenerate. The field of stem cell biology has only grown and HSCTs are able to be transplanted now to recipients to help a variety of diseases.
    [Show full text]
  • Hematopoietic Stem Cell Therapy) in MS
    FAQ About HSCT (Hematopoietic Stem Cell Therapy) in MS There is growing evidence that autologous HSCT is not for everyone with MS but may be highly effective for people with relapsing MS who meet very specific characteristics. The National Medical Advisory Committee of the National MS Society has written an article reviewing evidence related to the optimal use of autologous hematopoietic stem cell transplantation (aHSCT, commonly known as bone marrow transplants) for the treatment of specific types of relapsing multiple sclerosis. The committee’s findings are published in JAMA Neurology (online October 26, 2020). Q. What is HSCT for multiple sclerosis? A. HSCT (Hematopoietic Stem Cell Transplantation) attempts to “reboot” the immune system, which is responsible for damaging the brain and spinal cord in MS. In HSCT for MS, hematopoietic (blood cell-producing) stem cells, which are derived from a person’s own (“autologous”) bone marrow or blood, are collected and stored, and the rest of the individual’s immune cells are depleted by chemotherapy. Then the stored hematopoietic stem cells are reintroduced to the body. The new stem cells migrate to the bone marrow and over time produce new white blood cells. Eventually they repopulate the body with immune cells. Q. What is the idea behind autologous HSCT (aHSCT) for MS? A. The goal of aHSCT is to reset the immune system and stop the inflammation that contributes to active relapsing MS. Q. Is aHSCT an FDA-approved therapy option for people with MS? A. The medications and procedures used in aHSCT are already approved by the FDA. Publication of the outcomes from well-controlled clinical studies of aHSCT therapy will encourage greater acceptance and use by the medical community.
    [Show full text]
  • For Inflammatory Bowel Disease
    250 NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE INTERVENTIONAL PROCEDURES PROGRAMME Interventional procedures overview of leukapheresis (white cell apheresis) for inflammatory bowel disease Introduction This overview has been prepared to assist members of the Interventional Procedures Advisory Committee (IPAC) in making recommendations about the safety and efficacy of an interventional procedure. It is based on a rapid review of the medical literature and specialist opinion. It should not be regarded as a definitive assessment of the procedure. Date prepared This overview was prepared in August 2004. Procedure names • Leukapheresis • White cell apheresis. • Leukocyte removal therapy. • Selective granulocyte and monocyte adsorption apheresis. • Leukocytapheresis. Specialty society • British Society of Gastroenterology. Description Indications Inflammatory bowel disease. Ulcerative colitis and Crohn’s disease are the most common forms of inflammatory bowel disease. Ulcerative colitis causes inflammation and ulceration of the rectum and sometimes the colon. Symptoms include bloody diarrhoea and rectal bleeding. Crohn’s disease usually causes inflammation and ulceration of the small and large intestines, but it can affect any part of the digestive tract. The main symptoms are abdominal pain, diarrhoea and weight loss. Both of these are chronic conditions, characterised by periods of clinical relapse and remission. The incidence of ulcerative colitis is around 10 to 20 per 100,000 per year in the UK and the incidence of Crohn’s disease is approximately 5 to 10 per 100,000 per year.1 Current treatment and alternatives Conservative treatments include dietary measures, and medications to control inflammation. Immunosuppressants may be used if other medical therapies are ineffective at maintaining remission. Patients with ulcerative colitis that does not respond to medical therapy may be treated with surgery to remove the colon.
    [Show full text]
  • Reference Ranges for Blood Concentrations of Eosinophils And
    Journal of Perinatology (2010) 30, 540–545 r 2010 Nature America, Inc. All rights reserved. 0743-8346/10 www.nature.com/jp ORIGINAL ARTICLE Reference ranges for blood concentrations of eosinophils and monocytes during the neonatal period defined from over 63 000 records in a multihospital health-care system RD Christensen1,2, J Jensen1,3, A Maheshwari4 and E Henry1,3 1Intermountain Healthcare Women and Newborns Clinical Program, Ogden, UT, USA; 2McKay-Dee Hospital Center, Ogden, UT, USA; 3Institute for Healthcare Delivery Research, Salt Lake City, UT, USA and 4Divisions of Neonatology and Pediatric Gastroenterology, Departments of Pediatrics, Cell Biology, and Pathology, University of Alabama at Birmingham, Birmingham, AL, USA Introduction Objective: Blood concentrations of eosinophils and monocytes are part Normal values for hematological parameters are not generally of the complete blood count. Reference ranges for these concentrations during available for neonates because blood is not drawn on healthy the neonatal period, established by very large sample sizes and modern neonates to establish normal ranges. Instead, ‘reference ranges’ are methods, are needed for identifying abnormally low or high values. used in neonatal hematology.1–6 These consist of the 5th to 95th Study Design: We constructed reference ranges for eosinophils per ml percentile values assembled from large numbers of neonates with and monocytes per ml among neonates of 22 to 42 weeks of gestation, minimal pathology or with pathology not thought to be relevant to on the day of birth, and also during 28 days after birth. Data were the laboratory parameter under study. Recent examples of their obtained from archived electronic records over an eight and one-half-year usefulness include the following: Reference ranges for erythrocyte period in a multihospital health-care system.
    [Show full text]
  • IDF Guide to Hematopoietic Stem Cell Transplantation
    Guide to Hematopoietic Stem Cell Transplantation Immune Deficiency Foundation Guide to Hematopoietic Stem Cell Transplantation This publication contains general medical information that cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this publication should not be used as a substitute for professional medical advice. In all cases, patients and caregivers should consult their healthcare providers. Each patient’s condition and treatment are unique. Copyright 2018 by Immune Deficiency Foundation, USA Readers may redistribute this guide to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. Immune Deficiency Foundation Guide to Hematopoietic Stem Cell Transplantation may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from the Immune Deficiency Foundation (IDF). If you have any questions about permission, please contact: Immune Deficiency Foundation, 110 West Road, Suite 300, Towson, MD 21204, USA, or by telephone: 800-296-4433. For more information about IDF, go to: www.primaryimmune.org. This publication has been made possible through the IDF SCID Initiative and the SCID, Angels for Life Foundation. Acknowledgements The Immune Deficiency Foundation would like to thank the organizations and individuals who helped make this publication possible and contributed to the development of the Immune Deficiency Foundation Guide to Hematopoietic Stem
    [Show full text]
  • Stem Cell Hematopoiesis
    Hematopoietic and Lymphoid Neoplasm Project Introduction to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues 4th edition 2 Hematopoietic and Lymphoid Lineages, Part I Steven Peace, CTR Westat September 2009 3 Objectives • Understand stem cell hematopoiesis • Understand proliferation • Understand differentiation • Provide a History of Classification of Tumors of Hematopoietic and Lymphoid Tissues • Understand the delineation of cell lines (lineage) in relation to the WHO Classification 4 Objectives (2) • Introduce WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, 4th ed. • Introduce NEW ICD-O histology codes • Introduce NEW reportable conditions 5 Stem Cell Hematopoiesis • What is a hematopoietic stem cell? • Where are hematopoietic stem cells found? • What is Hematopoiesis? • Hematopoietic stem cells give rise to ALL blood cell types including; • Myeloid lineages • Lymphoid lineages 6 Hematopoietic stem cells give rise to two major progenitor cell lineages, myeloid and lymphoid progenitors Regenerative Medicine, 2006. http://www.dentalarticles.com/images/hematopoiesis.png 7 Proliferation and Differentiation • Regulation of proliferation • Regulation of differentiation • Both affect development along cell line • Turn on/Turn off • Growth factors • Genes (including mutations) • Proteins • Ongogenesis – becoming malignant 8 Blood Lines – Donald Metcalf, AlphaMED Press, 2005 Figure 3.2 The eight major hematopoietic lineages generated by self-renewing multipotential stem cellsB Copyright © 2008 by AlphaMed
    [Show full text]
  • Generation of Monocyte-Derived Tumor-Associated Macrophages Using
    Benner et al. Journal for ImmunoTherapy of Cancer (2019) 7:140 J Immunother Cancer: first published as 10.1186/s40425-019-0622-0 on 28 May 2019. Downloaded from https://doi.org/10.1186/s40425-019-0622-0 RESEARCHARTICLE Open Access Generation of monocyte-derived tumor- associated macrophages using tumor- conditioned media provides a novel method to study tumor-associated macrophages in vitro Brooke Benner1, Luke Scarberry1, Lorena P. Suarez-Kelly2, Megan C. Duggan1, Amanda R. Campbell1, Emily Smith1, Gabriella Lapurga1, Kallie Jiang1, Jonathan P. Butchar1, Susheela Tridandapani1, John Harrison Howard2, Robert A. Baiocchi3, Thomas A. Mace1 and William E. Carson III1,2* Abstract Background: Tumor-associated macrophages (TAM) are expanded and exhibit tumor-promoting properties within the tumor microenvironment. Current methods to study TAM have not been replicated across cancer types and often do not include exogenous growth factors from the tumor, a key factor in TAM differentiation in vivo. Methods: In this study, an in vitro method to generate monocyte- derived TAM using tumor- conditioned media (TCM) and a cytokine cocktail containing IL-4, IL-10, and M-CSF was utilized to study the phenotype, morphology, and function of TAM across multiple cancer types. TCM was generated from two breast cancer cell lines and an Epstein-Barr virus-positive lymphoma cell line. The properties of in vitro generated TAM were compared to in vitro generated M1 and M2- like macrophages and TAM isolated from patients with cancer. Results: TAM generated in this fashion displayed an increase in CD163/CD206 co-expression compared to M2- like http://jitc.bmj.com/ macrophages (87 and 36%, respectively).
    [Show full text]
  • Immune Effector Monocyte–Neutrophil Cooperation Induced by the Primary Tumor Prevents Metastatic Progression of Breast Cancer
    Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer Catharina Hagerlinga,b,1,2, Hugo Gonzaleza,3, Kiarash Salaria,3, Chih-Yang Wanga,4, Charlene Lina, Isabella Roblesa, Merel van Gogha, Annika Dejmekc, Karin Jirströmb, and Zena Werba,d,2 aDepartment of Anatomy, University of California, San Francisco, CA 94143-0452; bDepartment of Clinical Sciences, Division of Clinical Oncology and Pathology, Lund University, SE-221 85 Lund, Sweden; cDepartment of Translational Medicine, Lund University, Malmö SUS, SE-214 21 Malmö, Sweden; and dHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143 Contributed by Zena Werb, August 30, 2019 (sent for review May 3, 2019; reviewed by Yves DeClerck and Mikala Egeblad) Metastatic behavior varies significantly among breast cancers. Mech- patients’ breast cancer tumors and is hence an attractive preclinical anisms explaining why the majorityofbreastcancerpatientsnever model to find novel therapeutic alternatives for metastatic breast develop metastatic outgrowth are largely lacking but could underlie cancer (12). We furthermore validated our PDX-derived findings the development of novel immunotherapeutic target molecules. Here with a large primary breast cancer tissue microarray (TMA), pleural we show interplay between nonmetastatic primary breast cancer effusions from breast cancer patients and an immunocompetent and innate immune response, acting together to control metastatic syngeneic mammary cancer model. Taken together, we reveal in- progression. The primary tumor systemically recruits IFNγ-producing terplay between the primary breast cancer tumor and myeloid im- immune effector monocytes to the lung. IFNγ up-regulates Tmem173/ mune response, acting together to control metastatic progression.
    [Show full text]
  • Basophils Trigger Emphysema Development in a Murine Model of COPD Through IL-4–Mediated Generation of MMP-12–Producing Macrophages
    Basophils trigger emphysema development in a murine model of COPD through IL-4–mediated generation of MMP-12–producing macrophages Sho Shibataa,b, Kensuke Miyakea, Tomoya Tateishib, Soichiro Yoshikawaa, Yoshinori Yamanishia, Yasunari Miyazakib, Naohiko Inaseb, and Hajime Karasuyamaa,1 aDepartment of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan; and bDepartment of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan Edited by Kazuhiko Yamamoto, the University of Tokyo; Max Planck–The University of Tokyo Center for Integrative Inflammology, the University of Tokyo, Tokyo, Japan, and accepted by Editorial Board Member Tadatsugu Taniguchi November 2, 2018 (received for review August 13, 2018) Chronic obstructive pulmonary disease (COPD) is a leading cause of COPD even after smoking has stopped (9). As an alternative morbidity and mortality worldwide. It has generally been consid- approach, a protease-induced model was established (10) soon ered a non-Th2-type lung disorder, characterized by progressive after the discovery of the association between α1-antitrypsin airflow limitation with inflammation and emphysema, but its deficiency and emphysema in humans (11), implying that an im- cellular and molecular mechanism remains ill defined, compared balance between proteases and antiproteases in the lung may re- with that of asthma characterized by reversible airway obstruc- sult in emphysema formation. Intratracheal or intranasal instillation tion. Here we show a previously unappreciated role for basophils of elastolytic enzymes, such as papain, human neutrophil elastase, at the initiation phase of emphysema formation in an elastase- and porcine pancreatic elastase, is utilized to trigger emphysema induced murine model of COPD in that basophils represent less formation (10, 12, 13).
    [Show full text]
  • Cell Division History Determines Hematopoietic Stem Cell Potency Fumio Arai1,†,*, Patrick S
    bioRxiv preprint doi: https://doi.org/10.1101/503813; this version posted January 15, 2019. 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. Cell Division History Determines Hematopoietic Stem Cell Potency Fumio Arai1,†,*, Patrick S. Stumpf2,†, Yoshiko M. Ikushima3,†, Kentaro Hosokawa1, Aline Roch4, Matthias P. Lutolf4, Toshio Suda5, and Ben D. MacArthur2,6,7,* †† 1Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan. 2Centre for Human Development, Stem Cells and Regeneration, University of Southampton, SO17 1BJ, UK 3Research Institute National Center for Global Health and Medicine, Tokyo, Japan 4Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland 5Cancer Science Institute, National University of Singapore, 14 Medical Drive, MD6, 117599 Singapore, Singapore 6Institute for Life Sciences, University of Southampton, SO17 1BJ, United Kingdom 7Mathematical Sciences, University of Southampton, SO17 1BJ, United Kingdom *Correspondence to Fumio Arai ([email protected]) and Ben MacArthur ([email protected]) †These authors contributed equally. ††Lead Author ABSTRACT Loss of stem cell self-renewal may underpin aging. Here, we combined single cell profiling, deep-learning, mathematical modelling and in vivo functional studies to explore how hematopoietic stem cell (HSC) division patterns evolve with age. We trained an artificial neural network (ANN) to accurately identify cell types in the hematopoietic hierarchy and predict their age from their gene expression patterns.
    [Show full text]
  • Understanding the Immune System: How It Works
    Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them.
    [Show full text]
  • Neutrophil and Monocyte Adhesion Molecules in Bronchopulmonary
    F76 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/fn.89.1.F76 on 1 January 2004. Downloaded from ORIGINAL ARTICLE Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids P Ballabh, M Simm, J Kumari, A N Krauss, A Jain, C Califano, M L Lesser, S Cunningham-Rundles ............................................................................................................................... Arch Dis Child Fetal Neonatal Ed 2004;89:F76–F83 Aims: To study a longitudinal change in the expression of adhesion molecules CD11b, CD18, and CD62L on neutrophils and monocytes in very low birth weight babies who develop respiratory distress syndrome, to compare these levels between bronchopulmonary dysplasia (BPD) and non-BPD infants, and to assess the effect of corticosteroid treatment on these adhesion molecules. See end of article for authors’ affiliations Methods: Of 40 eligible neonates, 11 neonates were oxygen dependent at 36 weeks (BPD 36 weeks), 16 ....................... infants were oxygen dependent at 28 days, but not at 36 weeks (BPD d28), and 13 infants did not develop BPD. Seventeen neonates received a six day course of steroid treatment. Expression of CD11b, CD18, and Correspondence to: Dr P Ballabh, Assistant CD62L was measured on neutrophils and monocytes in arterial blood on days 1, 3, 7, 14, 21, and 28, Professor, Division of and before and 2–3 days after initiation of dexamethasone treatment by flow cytometry. Neonatology, Department Results: CD18 expression on neutrophils and monocytes and CD62L on neutrophils, measured as mean of Pediatrics, NICU, 2nd fluorescent intensity, was significantly decreased in BPD neonates compared to non-BPD neonates on days Floor, Main Building, Westchester Medical 1–28.
    [Show full text]