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Neutrophil extracellular traps

Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
Cédric Seignez, Mia Phillipson
PURPOSE OF REVIEW: This review describes the mechanisms by which neutrophils contribute to angiogenesis in hypoxic tissues during different conditions and diseases (e.g., menstrual cycle, wound healing, ischemic diseases, cancers), with particular focus on the recently described proangiogenic neutrophil subpopulation. RECENT FINDINGS: The importance of neutrophils in initiation of angiogenesis has been described during the past decade, and is believed to occur through release of the well-known proangiogenic factors Bv8, vascular endothelial growth factor A, and matrix metalloproteinase 9...
October 15, 2016: Current Opinion in Hematology
Bryant R England, Geoffrey M Thiele, Ted R Mikuls
PURPOSE OF REVIEW: This article reviews recent literature on the origin and pathogenic role of anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). RECENT FINDINGS: ACPAs and ACPA-immune complexes interact with immune cells to facilitate articular inflammation. Findings from recent in vitro and in vivo studies are congruent with epidemiologic observations in RA supporting a pathogenic role of ACPAs. SUMMARY: ACPAs target proteins/peptides with citrullinated epitopes and serve as informative RA biomarkers...
October 13, 2016: Current Opinion in Rheumatology
Yaíma L Lightfoot, Mariana J Kaplan
PURPOSE OF REVIEW: A breakdown of immune tolerance to self-antigens in a genetically predisposing background, precipitated by environmental triggers, contributes to the development of systemic autoimmune diseases. Renewed interest in the immunomodulatory capabilities of neutrophils in systemic autoimmunity has identified neutrophil extracellular trap (NET) formation as a distinguishing action of neutrophils in afflicted hosts. RECENT FINDINGS: Oxidation of nucleic acids and posttranslational modifications of proteins distinctly occur during NET formation and may promote enhanced immunogenicity...
October 13, 2016: Current Opinion in Rheumatology
Francesca Tamarozzi, Joseph D Turner, Nicolas Pionnier, Angela Midgley, Ana F Guimaraes, Kelly L Johnston, Steven W Edwards, Mark J Taylor
The endosymbiotic bacteria, Wolbachia, induce neutrophilic responses to the human helminth pathogen Onchocerca volvulus. The formation of Neutrophil Extracellular Traps (NETs), has been implicated in anti-microbial defence, but has not been identified in human helminth infection. Here, we demonstrate NETs formation in human onchocerciasis. Extracellular NETs and neutrophils were visualised around O. volvulus in nodules excised from untreated patients but not in nodules from patients treated with the anti-Wolbachia drug, doxycycline...
October 18, 2016: Scientific Reports
Tetsuo Nakayama
The humoral and cellular immune responses of adaptive immunity are induced following immunization with effective vaccines. They induce functional cytokines and chemokines through the binding of vaccine components or adjuvants to innate immune receptors. Alum-adjuvanted vaccines induce local inflammatory nodules at injection sites, and the systemic and local production of the inflammatory cytokines, IL-1β, IL-6, and TNF-α, has been reported to occur three hours after vaccinations. Furthermore, G-CSF levels increase at injection sites...
October 13, 2016: Vaccine
M Batinica, A Stephan, J Steiger, I Tantcheva-Poόr, S A Eming, M Fabri
Neutrophils eject neutrophil extracellular traps (NETs), complexes of DNA and proteins [1]. As NETs contain antimicrobial proteins, they have been implicated in host defence [1, 2]. Moreover, NETs trigger inflammation [2, 3]. Reactive oxygen species (ROS)-dependent (e.g. by phorbol myristate acetate (PMA)) and ROS-independent (e.g. by calcium ionophore (CaI)) inducers of NETosis have been described [2]. This article is protected by copyright. All rights reserved.
October 12, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Paul Hasler, Stavros Giaglis, Sinuhe Hahn
Polymorphonuclear neutrophil granulocytes are the first responders of the immune system to threats by invading microorganisms. In the traditional view, they combat the intruders by phagocytosis and externalisation of granules containing lytic and microbicidal factors. A dozen years ago, this concept was expanded by the observation that neutrophils may react to bacteria by extruding their nuclear chromosomal DNA with attached nuclear and cytoplasmic constituents to form extracellular reticular structures. Since they trapped and immobilised the microbes, they were designated neutrophil extracellular traps (NETs), and their ensuing cell death NETosis...
2016: Swiss Medical Weekly
Erik Tenland, Gisela Håkansson, Nader Alaridah, Nataliya Lutay, Anna Rönnholm, Oskar Hallgren, Gunilla Westergren-Thorsson, Gabriela Godaly
Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells...
2016: PloS One
Anna-Karin Olsson, Jessica Cedervall
It has become increasingly clear that circulating immune cells in the body have a major impact on cancer development, progression, and outcome. The role of both platelets and neutrophils as independent regulators of various processes in cancer has been known for long, but it has quite recently emerged that the platelet-neutrophil interplay is yet a critical component to take into account during malignant disease. It was reported a few years ago that neutrophils in mice with cancer have increased propensity to form neutrophil extracellular traps (NETs) - web-like structures formed by externalized chromatin and secreted proteases...
2016: Frontiers in Immunology
Hyun Ju Yoo, Jee-Soo Lee, Ji-Eun Kim, JaYoon Gu, Youngil Koh, Inho Kim, Hyun Kyung Kim
INTRODUCTION: When leukocytes are stimulated by reactive oxygen species (ROS), they release nuclear contents into the extracellular milieu, called by extracellular traps (ET). The nuclear contents are mainly composed of the histone-DNA complex and neutrophil elastase. This study investigated whether leukemic cells could release ET and the released histone could induce endothelial activation, eventually resulting in leukemic progression. METHODS: The circulating ET were measured in 80 patients with hematologic diseases and 40 healthy controls...
2016: PloS One
Jennifer L Johnson, Mahalakshmi Ramadass, Jing He, Steven J Brown, Jinzhong Zhang, Lusine Abgaryan, Nikolaos Biris, Evripidis Gavathiotis, Hugh Rosen, Sergio D Catz
Neutrophils constitute the first line of cellular defense in response to bacterial and fungal infections and rely on granular proteins to kill microorganisms, but uncontrolled secretion of neutrophil cargos is injurious to the host and should be closely regulated. Thus, increased plasma levels of neutrophil secretory proteins including myeloperoxidase and elastase is associated with tissue damage and is a hallmark of systemic inflammation. Here, we describe a novel high-throughput screening approach to identify small-molecule inhibitors of the interaction between the small GTPase Rab27a and its effector JFC1, two central regulators of neutrophil exocytosis...
October 4, 2016: Journal of Biological Chemistry
Quinte Braster, Carlos Silvestre Roig, Helene Hartwig, Linda Beckers, Myrthe den Toom, Yvonne Döring, Mat J Daemen, Esther Lutgens, Oliver Soehnlein
Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation...
2016: PloS One
Günther Schönrich, Martin J Raftery
Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils...
2016: Frontiers in Immunology
Xian M O'Brien, Jonathan S Reichner
Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate toward a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome...
2016: Frontiers in Immunology
He Meng, Srilakshmi Yalavarthi, Yogendra Kanthi, Levi F Mazza, Megan A Elfline, Catherine E Luke, David J Pinsky, Peter K Henke, Jason S Knight
OBJECTIVE: Antiphospholipid syndrome (APS) is a leading acquired cause of thrombotic events. While antiphospholipid antibodies have been shown to promote thrombosis in mice, the role of neutrophils has not been explicitly studied. Here, we characterized neutrophils in the context of a new model of antiphospholipid antibody-mediated venous thrombosis. METHODS: Mice were administered IgG fractions prepared from patients with APS. At the same time, flow through the inferior vena cava was reduced by a standard stenosis...
October 1, 2016: Arthritis & Rheumatology
Marcel P B Jansen, Diba Emal, Gwendoline J D Teske, Mark C Dessing, Sandrine Florquin, Joris J T H Roelofs
Acute kidney injury is often the result of ischemia reperfusion injury, which leads to activation of coagulation and inflammation, resulting in necrosis of renal tubular epithelial cells. Platelets play a central role in coagulation and inflammatory processes, and it has been shown that platelet activation exacerbates acute kidney injury. However, the mechanism of platelet activation during ischemia reperfusion injury and how platelet activation leads to tissue injury are largely unknown. Here we found that renal ischemia reperfusion injury in mice leads to increased platelet activation in immediate proximity of necrotic cell casts...
September 27, 2016: Kidney International
Ine Jorgensen, Joseph P Lopez, Stefan A Laufer, Edward A Miao
Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore-induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT, with its associated bacteria, by neutrophils; bacteria are subsequently killed via neutrophil ROS...
September 28, 2016: European Journal of Immunology
Takanori Onouchi, Kazuya Shiogama, Takahiro Matsui, Yasuyoshi Mizutani, Kouhei Sakurai, Ken-Ichi Inada, Yutaka Tsutsumi
Neutrophil extracellular traps (NETs) represent an extracellular, spider's web-like structure resulting from cell death of neutrophils. NETs play an important role in innate immunity against microbial infection, but their roles in human pathological processes remain largely unknown. NETs and fibrin meshwork both showing fibrillar structures are observed at the site of fibrinopurulent inflammation, as described in our sister paper [Acta Histochem. Cytochem. 49; 109-116, 2016]. In the present study, immunoelectron microscopic study was performed for visualizing NETs and fibrin fibrils (thick fibrils in our tongue) in formalin-fixed, paraffin-embedded sections of autopsied lung tissue of legionnaire's pneumonia...
August 30, 2016: Acta Histochemica et Cytochemica
Kazuya Shiogama, Takanori Onouchi, Yasuyoshi Mizutani, Kouhei Sakurai, Ken-Ichi Inada, Yutaka Tsutsumi
Neutrophil extracellular traps (NETs) are extracellular fibrillary structures composed of degraded chromatin and granules of neutrophil origin. In fibrinopurulent inflammation such as pneumonia and abscess, deposition of fibrillar eosinophilic material is a common histopathological finding under hematoxylin-eosin staining. Expectedly, not only fibrin fibrils but also NETs consist of the fibrillar material. The aim of the present study is to analyze immunohistochemically how NETs are involved in the inflammatory process...
August 30, 2016: Acta Histochemica et Cytochemica
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