DOCSLIB.ORG

Neutrophil and Monocyte Toll-Like Receptor 4, Cd11b and Reactive Oxygen Intermediates, and Neuroimaging Outcomes in Preterm Infants

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neutrophil and Monocyte Toll-Like Receptor 4, Cd11b and Reactive Oxygen Intermediates, and Neuroimaging Outcomes in Preterm Infants nature publishing group Articles Clinical Investigation Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants Fiona M. O’Hare1–4, William Watson2,3, Amanda O’Neill2,3, Tim Grant2,3, Chike Onwuneme1–4, Veronica Donoghue1,5, Eoghan Mooney6, Paul Downey6, John Murphy1, Anne Twomey1 and Eleanor J. Molloy1–3,7–9 BACKGROUND: Activated leukocytes and infection are impli- who died with white matter injury (5) (see Supplementary cated in neonatal brain injury. Leukocyte surface receptors References 11–14 online). Postnatal infection also contributes are increased in stroke models and may be targets for future to the development of PVL and CP (6,7). Inhibiting inflamma- adjunctive therapies. tory responses may decrease secondary brain injury following METHODS: Serial blood samples were analyzed from preterm infection or hypoxia–ischemia (8) and recently tertiary brain infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life. injury has been described as a possible mechanism of preterm Monocyte and neutrophil activation were evaluated via flow brain injury with persistent long-term inflammation (9). We cytometry at baseline and following endotoxin stimulation ex were interested in the systemic inflammatory response in new- vivo by measuring CD11b (activation), toll-like receptor 4 (TLR- born infants at risk of brain injury by examining markers of 4; endotoxin recognition) expression, and intracellular reactive activation of monocytes and neutrophils. oxygen intermediate (ROI) production (function). Reactive oxygen intermediate (ROI) generation is essential RESULTS: Control preterm infants with normal neuroimaging for neutrophil intracellular killing of invading microorganisms had elevated baseline CD11b and TLR-4 expression and ROI following phagocytosis. ROIs are a major mechanism of innate production compared with adults as well as a robust immune antimicrobial host defense (see Supplementary Reference 15 response following endotoxin stimulation. Preterm infants online) but can cause damage by oxidizing membrane phos- with abnormal neuroimaging had increased neutrophil TLR-4 pholipids, proteins, nucleic acids, and nucleotides (10). We and ROI compared with all controls. studied ROI production as a marker of immune cell func- CONCLUSION: Preterm infants have a robust immune tion. CD11b is a receptor on the cell surface that is important response compared with adults. Increased TLR-4 expression for neutrophil and monocyte migration to sites of infection/ in preterm infants with abnormal neuroimaging is similar to inflammation. Neonatal neutrophil migration is decreased at findings in adult stroke. In addition, ROI production may cause birth due to decreased total cell content of CD11b and issues tissue injury. The modulation of these responses may be ben- related to its cell surface translocation. Although baseline eficial in preterm inflammatory disorders. CD11b expression is reported to be similar to that of adults, neonates are unable to upregulate CD11b expression to the same magnitude following lipopolysaccharide (LPS) stimula- reterm infants are susceptible to inflammatory disorders tion, especially in preterm infants (11). The key receptor for Presulting in multiorgan dysfunction (1). Systemic inflam- recognizing endotoxin on the immune cell surface is toll-like mation may be the final common pathway for insults caused receptor 4 (TLR-4). Healthy neonates have similar basal TLR-4 by both hypoxia–ischemia and infection in these infants and expression to adults. Both term and preterm neonates increase may be associated with brain injury (2) (see Supplementary TLR-4 expression in response to LPS. Responses to LPS are Reference 1 online). Many studies demonstrate an asso- determined by the level of TLR-4 expressed, and overexpres- ciation between maternal/fetal infection and periventricu- sion can lead to uncontrolled inflammation resulting in dam- lar leukomalacia (PVL) detected on cranial ultrasound (3) age to healthy tissues. Shen et al. (12) showed a rapid increase (see Supplementary References 2–5 online), or the later in TLR-2 and TLR-4 expression over the first month of life but development of cerebral palsy (CP) (4) (see Supplementary no parallel increase in LPS-induced cytokine production. References 6–10 online). Elevated cytokines have been We hypothesized that markers of neutrophil and monocyte detected histologically in the brains of preterm infants activation may be altered in preterm infants with abnormal 1Department of Paediatrics, National Maternity Hospital, Dublin 2, Ireland; 2University College Dublin School of Medicine and Medical Sciences, Dublin, Ireland; 3University College Dublin Conway Institute of Biomolecular and Biomedical Sciences, Dublin, Ireland; 4National Children’s Research Centre, Dublin, Ireland; 5Department of Radiology, Children’s University Hospital, Dublin, Ireland; 6Department of Pathology, National Maternity Hospital, Dublin 2, Ireland; 7Department of Neonatology, Our Lady’s Children’s Hospital, Dublin, Ireland; 8Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland; 9Department of Paediatrics, Trinity College Dublin, University of Dublin, Dublin, Ireland. Correspondence: Eleanor J. Molloy ([email protected]) Received 12 February 2014; accepted 5 January 2015; advance online publication 20 May 2015. doi:10.1038/pr.2015.66 82 Pediatric REsEarcH Volume 78 | Number 1 | July 2015 Copyright © 2015 International Pediatric Research Foundation, Inc. Preterm immune function and brain injury Articles neuroimaging. We examined markers of monocyte and neu- Table 1. Demographic variables trophil function and activation (CD11b (activation), TLR-4 Preterm infants’ expression (LPS recognition), and ROI production (function)) neuroimaging outcome serially over the first week of life and correlated our findings Characteristics Normal Abnormal P value with neuroimaging. Neonatal Gestational age (weeks+days) 28+6 ± 1+6 28+3 ±1+6 0.519 RESULTS (mean ± SD) Patient Demographics Gestational age, <28/40 (N (%)) 12 (32) 6 (43) 0.487 Fifty-one preterm infants born <32 wk gestation were included, and three infants died (normal neuroimaging n = 40; Gestational age, >28/40 (N (%)) 25 (68) 8 (57) 0.487 abnormal neuroimaging/ Death (RIP); n = 11). A total of 404 Birth weight (grams) (mean ± SD) 1,178 ± 324 1,117 ± 305 0.542 samples were processed. There were no differences in gender Sex (N (%)) (male) 27 (73) 11 (79) 0.492 distribution, preeclampsia, prolonged rupture of membranes, SVD (N (%))(mean ± SD) 10 (28) 3 (21) 0.646 maternal pyrexia, histological chorioamnionitis, surfactant Emergency CSxn (N (%)) 26 (70) 11 (79) 0.741 treatment, gestational age, birth weight, mode of delivery, doses of antenatal steroids received, Apgar scores, cord or admission Antenatal steroids, one dose (N (%)) 8 (22) 4 (29) 0.737 blood gas parameters, nasal continuous positive airway pres- Antenatal steroids, two doses (N (%)) 28 (76) 10 (71) 0.737 sure (CPAP) hour, or duration of intubation, between preterm Apgar score at 1 min (mean ± SD) 6 (3) 7 (2) 0.512 neonates with normal and abnormal neuroimaging (Table 1). Apgar score at 5 min (mean ± SD) 8 (2) 9 (1) 0.092 There was a statistically significant difference in mortality (n Cord pH 7.33±0.05 7.31±0.09 0.395 (%)) observed between the two groups: normal vs. abnormal neuroimaging 0 (0) vs. 3 (21) (P = 0.04). Cord base excess −2.7 ± 2.8 −5.6 ± 3.1 0.088 All infants had serial cranial ultrasounds, and 29 infants Admission gas, pH (mean ± SD) 7.27 ± 0.10 7.24 ± 0.14 0.315 had a magnetic resonance imaging (MRI) brain at term cor- Admission gas, base excess −3.7 ± 4.1 −5.5 ± 4.1 0.196 rected age. MRI was scored according to the Inder criteria (6) (mean ± SD) independently by a consultant Pediatric Radiologist. Twenty Admission gas, lactate 4.5 ± 1.4 6.4 ± 2.5 0.502 infants had completely normal imaging (white matter (WM) (mean ± SEM) score = 5–6; gray matter (GM) score 3–5). Nine infants had Chorioamnionitis (N (%)) 7 (19) 0 (0) 0.080 evidence of WM abnormality (mild = 4: WM score 7–9; mod- Surfactant (N (%)) 13 (35) 5 (36) 0.824 erate = 3: WM score 10–12; severe = 2: WM score 13–15). One nCPAP hours (mean ± SD) 0.688 infant had both WM and GM abnormality (GM score 6–9; 197 ± 43 162 ± 81 Tables 2 and 3). Twenty-two infants had only cranial ultra- Hours intubated (mean ± SEM) 162 ± 63 88 ± 25 0.432 sound imaging. No abnormality was detected in 14 infants. CLD (N (%)) 8 (20) 1 (9) 0.401 Evidence of intraventricular hamorrhage (IVH) was detected NEC (N (%)) 3 (8) 1 (9) 0.880 in five infants (grade 1 = 4; grade 2 = 1). Three infants had RIP (N (%)) 0 (0) 3 (21) 0.040 increased echogenicity in the periventricular WM. CLD, chronic lung disease; CSxn, caesarean section; nCPAP, nasal continuous positive There were no other significant differences between the airway pressure; NEC, necrotizing enterocolitis; SVD, spontaneous vaginal delivery. study groups with respect to chronic lung disease, patent duc- tus arteriosus, necrotizing enterocolitis, retinopathy of prema- turity, late-onset sepsis (LOS), and number of septic episodes ROI production following ex vivo LPS stimulation. Higher lev- and antibiotic days. There were no significant differences in els of ROI production were seen in both preterm groups com- duration of intubation, intermittent positive pressure ventila- pared with adults following stimulation which was statistically tion, nasal CPAP or nasal prong oxygen hours required,
Load more

Recommended publications
  • 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]
  • 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]
  • Eosinophils but Not of Neutrophils Stimulates Effector Functions of Human Interaction with Secretory Component
    Interaction with Secretory Component Stimulates Effector Functions of Human Eosinophils But Not of Neutrophils This information is current as Youichi Motegi and Hirohito Kita of September 23, 2021. J Immunol 1998; 161:4340-4346; ; http://www.jimmunol.org/content/161/8/4340 Downloaded from References This article cites 49 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/161/8/4340.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 23, 2021 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 © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Interaction with Secretory Component Stimulates Effector Functions of Human Eosinophils But Not of Neutrophils1 Youichi Motegi and Hirohito Kita2 Eosinophils and their products are important in the pathophysiology of allergic inflammation in mucosal tissues. Secretory component bound to IgA mediates transepithelial transport of IgA and confers increased stability on the resultant secretory IgA; however, the effect of secretory component on the biologic activity of IgA is unknown.
    [Show full text]
  • Effect of Recombinant Granulocyte Colony-Stimulating Factor on Blood
    Original ..............Article Effect of Recombinant Granulocyte Colony-Stimulating Factor on Blood Neutrophil Concentrations among Patients with ‘‘Idiopathic Neonatal Neutropenia’’: A Randomized, Placebo-controlled Trial Sandra E. Juul, MD, PhD INTRODUCTION Robert D. Christensen, MD A severe but self-limited idiopathic variety of neutropenia, termed ‘‘idiopathic neonatal neutropenia’’, has been described among preterm infants.1,2 Neonates with this condition have several features in common, including the fact that no specific variety of OBJECTIVES: neutropenia is diagnosed, it often appears late in the clinical We previously described a severe, prolonged, idiopathic, but self-resolving, course, can be quite prolonged, and generally occurs in otherwise variety of neutropenia among preterm neonates. In the present study, we well infants.1,2 It is not clear whether this condition is a single sought to assess the marrow neutrophil reserves of these patients by entity or represents multiple disorders with the common feature of serially measuring blood neutrophils following the administration of severe but self-limited neutropenia. As neutropenia in preterm recombinant granulocyte colony-stimulating factor (rG-CSF) or placebo. infants can be a sign of incipient severe illness, particularly sepsis, STUDY DESIGN: this variety of neutropenia in the neonatal intensive care unit (NICU) often causes concern, and sometimes prompts evaluations Prospective, randomized trial of rG-CSF vs placebo for infants with for infection and repeated or prolonged
    [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]
  • Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed/Refractory NHL Or ALL
    cells Article Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed/Refractory NHL or ALL Felix Korell 1,*, Sascha Laier 2, Sandra Sauer 1, Kaya Veelken 1, Hannah Hennemann 1, Maria-Luisa Schubert 1, Tim Sauer 1, Petra Pavel 2, Carsten Mueller-Tidow 1, Peter Dreger 1, Michael Schmitt 1 and Anita Schmitt 1 1 Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany; [email protected] (S.S.); [email protected] (K.V.); [email protected] (H.H.); [email protected] (M.-L.S.); [email protected] (T.S.); [email protected] (C.M.-T.); [email protected] (P.D.); [email protected] (M.S.); [email protected] (A.S.) 2 Institute of Clinical Transfusion Medicine and Cell Therapy (IKTZ), 89081 Heidelberg, Germany; [email protected] (S.L.); [email protected] (P.P.) * Correspondence: [email protected] Received: 9 April 2020; Accepted: 13 May 2020; Published: 15 May 2020 Abstract: Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total of 75 unstimulated leukaphereses were analyzed including 45 aphereses in patients and 30 in healthy donors. Thereof, 41 adult patients with Non-Hodgkin’s lymphoma (85%) or acute lymphoblastic leukemia (15%) underwent leukapheresis for CAR-T cell production.
    [Show full text]
  • An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in Vitro
    fimmu-11-00532 April 24, 2020 Time: 17:59 # 1 ORIGINAL RESEARCH published: 28 April 2020 doi: 10.3389/fimmu.2020.00532 An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro Mareike Ohms, Sonja Möller and Tamás Laskay* Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany Neutrophils act as the first line of defense against invading pathogens. Although traditionally considered in context of their antimicrobial effector functions, the importance of tumor-associated neutrophils (TANs) in the development of cancer has become increasingly clear during the last decade. With regard to their high plasticity, neutrophils were shown to acquire an anti-tumorigenic N1 or a pro-tumorigenic N2 phenotype. Despite the urgent need to get a comprehensive understanding of the interaction of TANs with their tumor microenvironment, most studies still rely on murine tumor models. Here we present for the first time a polarization attempt to generate N1 and N2 neutrophils from primary human neutrophils in vitro. Our results underscore Edited by: that N1-polarized neutrophils have a pro-inflammatory phenotype characterized among Martin Herrmann, University Hospital Erlangen, Germany others by a higher level of intercellular adhesion molecule (ICAM)-1 and high secretion Reviewed by: of interferon (IFN)g-induced protein 10 (IP-10)/C-X-C motif chemokine 10 (CXCL10) Payel Sil, and tumor necrosis factor (TNF). Further, we demonstrate that neutrophils incubated National Institute of Environmental under a tumor-mimicking in vitro environment show a high cell surface expression of Health Sciences (NIEHS), United States C-X-C motif chemokine receptor 2 (CXCR2) and secrete high levels of interleukin (IL)- Mihaela Gadjeva, 8.
    [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]
  • What You Need to Know About Innate Immunity
    WhatWhat youyou needneed toto knowknow aboutabout innateinnate immunityimmunity JenniferJennifer KoKo MD,MD, PhDPhD ClevelandCleveland ClinicClinic Immunology/PathologyImmunology/Pathology andand LaboratoryLaboratory MedicineMedicine InnateInnate ImmunityImmunity FirstFirst lineline ofof defense,defense, immediateimmediate defensedefense DayDay toto dayday protectionprotection OnlyOnly whenwhen innateinnate defensedefense bypassed,bypassed, evadedevaded oror overwhelmedoverwhelmed isis adaptiveadaptive immunityimmunity requiredrequired NonNon--specificspecific RecognizeRecognize pathogenspathogens inin aa genericgeneric wayway DoesDoes notnot conferconfer longlong lastinglasting oror protectiveprotective immunityimmunity toto hosthost EvolutionarilyEvolutionarily older,older, foundfound inin primitiveprimitive organismsorganisms InnateInnate ImmunityImmunity andand InflammationInflammation 1)1) RespondRespond rapidlyrapidly toto tissuetissue damagedamage physicalphysical andand chemicalchemical barrierbarrier recruitmentrecruitment ofof immuneimmune cellscells toto sitesite ofof injuryinjury 2)2) LimitLimit spreadspread ofof infectioninfection identificationidentification andand removalremoval ofof foreignforeign substancessubstances activationactivation ofof thethe complementcomplement cascadecascade activationactivation ofof coagulationcoagulation cascadecascade 3)3) InitiateInitiate adaptiveadaptive immuneimmune responseresponse antigenantigen presentationpresentation andand cytokinecytokine productionproduction 4)4)
    [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]