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neutrophils thrombosis

Carsten Deppermann, Paul Kubes
The primary function of platelets is to patrol the vasculature and seal vessel breaches to limit blood loss. However, it is becoming increasingly clear that they also contribute to pathophysiological conditions like thrombosis, atherosclerosis, stroke and infection. Severe sepsis is a devastating disease that claims hundreds of thousands of lives every year in North America and is a major burden to the public health system. Platelet surface receptors like GPIb, αIIbβ3, TLR2 and TLR4 are involved in direct platelet-bacteria interactions...
October 18, 2016: Seminars in Immunology
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
Jacob Mareen, Jithendriya Madhukara
Lucio phenomenon (LP) or erythema necroticans is a rare type of reaction pattern found in untreated patients with diffuse non-nodular leprosy. It is important to distinguish this from vasculonecrotic erythema nodosum because thalidomide with high-dose steroids is the mainstay of treatment for the latter, whereas LP shows no response to thalidomide. We report a case of a 60-year-old man who presented with purpuric patches, hemorrhagic blisters, and ulcers over extremities of 15 days duration. On cutaneous examination, there were multiple stellate purpuric patches, hemorrhagic bullae, and deep necrotic ulcers, mainly over extremities...
September 2016: Indian Dermatology Online Journal
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
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
Natascha Luther, Fatemeh Shahneh, Melanie Brähler, Franziska Krebs, Sven Jäckel, Saravanan Subramaniam, Christian Stanger, Tanja Schönfelder, Bettina Kleis-Fischer, Christoph Reinhardt, Hans C Probst, Philip Wenzel, Katrin Schäfer, Christian Becker
RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and non-immune cell function, however their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation and inflammatory activity of T cells in deep vein thrombosis (DVT) and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4(+) and CD8(+) T cells infiltrate the thrombus and vein wall rapidly upon DVT induction and remain in the tissue throughout thrombus resolution...
October 5, 2016: Circulation Research
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
Minoo Shahidi
One of the key players in both hemostasis and thrombosis is von Willebrand factor (vWF), which demonstrates a duality between these two processes. Thrombus is structured by numerous elements, including endothelial cells, platelets, plasma proteins and shear stress alteration. In circulation, once a vessel wall is injured, collagen is exposed and platelets attach to the site of injury. Accordingly, vWF mediates adherence of platelets to the damaged vessel wall by binding both to the collagen and platelet receptor...
September 15, 2016: Advances in Experimental Medicine and Biology
Cheng Hock Toh, Yasir Alhamdi, Simon T Abrams
Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface...
November 2016: Annals of Laboratory Medicine
Konstantin Stark, Vanessa Philippi, Sven Stockhausen, Johanna Busse, Antonella Antonelli, Meike Miller, Irene Schubert, Parandis Hoseinpour, Sue Chandraratne, Marie-Luise von Brühl, Florian Gärtner, Michael Lorenz, Alessandra Agresti, Raffaele Coletti, Daniel J Antoine, Ralf Heermann, Kirsten Jung, Sven Reese, Iina Laitinen, Markus Schwaiger, Axel Walch, Markus Sperandio, Peter P Nawroth, Christoph Reinhardt, Sven Jäckel, Marco E Bianchi, Steffen Massberg
Deep venous thrombosis (DVT) is one of the most common cardiovascular diseases, but its pathophysiology remains incompletely understood. While sterile inflammation has recently been shown to boost coagulation during DVT, the underlying molecular mechanisms are not fully resolved, which could potentially identify new anti-inflammatory approaches to prophylaxis and therapy of DVT. Using a mouse model of venous thrombosis induced by flow reduction in the vena cava inferior we identified blood-derived high-mobility group box 1 protein (HMGB1) - a prototypical mediator of sterile inflammation - to be a master regulator of the prothrombotic cascade involving platelets and myeloid leukocytes fostering occlusive DVT formation...
August 29, 2016: Blood
Kelly L Singel, Brahm H Segal
Neutrophils are the first responders to infection and injury and are critical for antimicrobial host defense. Through the generation of reactive oxidants, activation of granular constituents and neutrophil extracellular traps, neutrophils target microbes and prevent their dissemination. While these pathways are beneficial in the context of trauma and infection, their off-target effects in the context of tumor are variable. Tumor-derived factors have been shown to reprogram the marrow, skewing toward the expansion of myelopoiesis...
September 2016: Immunological Reviews
C Pérez-Sánchez, M A Aguirre, P Ruiz-Limón, N Barbarroja, Y Jiménez-Gómez, I Arias de la Rosa, A Rodriguez-Ariza, E Collantes-Estévez, P Segui, F Velasco, M J Cuadrado, R Teruel, R González-Conejero, C Martínez, Ch López-Pedrera
MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors...
2016: Scientific Reports
Xavier Delabranche, Laure Stiel, François Severac, Anne-Cécile Galoisy, Laurent Mauvieux, Fatiha Zobairi, Thierry Lavigne, Florence Toti, Eduardo Anglès-Cano, Ferhat Meziani, Julie Boisramé-Helms
INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic-shock induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study...
August 2, 2016: Shock
David X Liu, Peter J Didier, Gail Plauche, Bapi Pahar
Providencia stuartii (P. stuartii) is an opportunistic pathogen and major concern in urinary catheter-related infections in human medicine. Here we report P. stuartii-induced septicemia in an eighteen-year-old, female India-origin Rhesus macaque with multiple traumatic wounds. The animal had neutrophilic leukocytosis, necrosuppurative meningoencephalitis, hypophysitis and bronchopneumonia with vasculitis, thrombosis, and clusters of extracellular Gram-negative bacilli. P. stuartii was isolated from the lesions of the brain and lung and confirmed by PCR and sequencing...
July 28, 2016: Journal of Medical Primatology
A Balkarli, A Kucuk, H Babur, F Erbasan
OBJECTIVE: With this retrospective study, we researched the effects of mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) on the activity of Behçet's disease and susceptibility to thrombosis. PATIENTS AND METHODS: One hundred eighty-six patients with Behçet's disease, who met the inclusion criteria, were separated into two groups: 120 patients had active Behçet's disease (Group I) and 66 patients with inactive Behçet's disease (Group II). 79 healthy subjects as controls were included in the study...
July 2016: European Review for Medical and Pharmacological Sciences
Agostina Carestia, Tomas Kaufman, Mirta Schattner
In addition to being key elements in hemostasis and thrombosis, platelets have an important role in the inflammatory and innate immune response. This activity is associated with their capability to recognize pathogens through the expression of toll-like receptors, the secretion of various cytokines, chemokines, and growth factors stored within their granules, and the expression of cell adhesion molecules that allows interaction with other immune cells, mainly neutrophils and monocytes. As part of the first line of defense, neutrophils control invading pathogens by phagocytosis, the release of antimicrobial proteins during degranulation, or through the formation of web-like structures named neutrophil extracellular traps (NETs)...
2016: Frontiers in Immunology
Koshu Okubo, Mako Kamiya, Yasuteru Urano, Hiroshi Nishi, Jan M Herter, Tanya Mayadas, Daigoro Hirohama, Kazuo Suzuki, Hiroshi Kawakami, Mototsugu Tanaka, Miho Kurosawa, Shinji Kagaya, Keiichi Hishikawa, Masaomi Nangaku, Toshiro Fujita, Matsuhiko Hayashi, Junichi Hirahashi
Neutrophils are central players in the innate immune system. They generate neutrophil extracellular traps (NETs), which protect against invading pathogens but are also associated with the development of autoimmune and/or inflammatory diseases and thrombosis. Here, we report that lactoferrin, one of the components of NETs, translocated from the cytoplasm to the plasma membrane and markedly suppressed NETs release. Furthermore, exogenous lactoferrin shrunk the chromatin fibers found in released NETs, without affecting the generation of oxygen radicals, but this failed after chemical removal of the positive charge of lactoferrin, suggesting that charge-charge interactions between lactoferrin and NETs were required for this function...
August 2016: EBioMedicine
Andrew S Kimball, Andrea T Obi, Jose A Diaz, Peter K Henke
Venous thrombosis (VT), a leading cause of morbidity and mortality worldwide, has recently been linked to neutrophil activation and release of neutrophil extracellular traps (NETs) via a process called NETosis. The use of various in vivo thrombosis models and genetically modified mice has more precisely defined the exact role of NETosis in the pathogenesis of VT. Translational large animal VT models and human studies have confirmed the presence of NETs in pathologic VT. Activation of neutrophils, with subsequent NETosis, has also been linked to acute infection...
2016: Frontiers in Immunology
Nirav Dhanesha, Prem Prakash, Prakash Doddapattar, Ira Khanna, Molly J Pollpeter, Manasa K Nayak, Janice M Staber, Anil K Chauhan
OBJECTIVE: von Willebrand factor (VWF), which is synthesized in endothelial cells and megakaryocytes, is known to worsen stroke outcome. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically different from the endothelial cell-derived VWF (EC-VWF). However, little is known about relative contribution of different pools of VWF in stroke. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF mice, Plt-VWF mice that lack ADAMTS13 in platelets and plasma (Plt-VWF/Adamts13(-/-)), and EC-VWF mice to determine relative contribution of different pools of VWF in stroke...
September 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Kévin Bouiller, Sylvain Audia, Hervé Devilliers, Evelyne Collet, Marie Hélène Aubriot, Vanessa Leguy-Seguin, Sabine Berthier, Philippe Bonniaud, Pascal Chavanet, Jean-François Besancenot, Pierre Vabres, Laurent Martin, Maxime Samson, Bernard Bonnotte
In this study, outcomes of patients with leukocytoclastic vasculitis (LCV) were analyzed focusing on clinical, histopathology and laboratory findings, relapses, and survival.Data from patients with cutaneous vasculitis diagnosed between January 1, 2000, and December 31, 2010, at Dijon University Hospital (France) were retrospectively reviewed. LCV was defined as perivascular neutrophilic infiltrate, endothelial cell nuclear swelling, extravasation of red blood cells, and/or fibrin deposition in vessels. Patients were classified according to the 2012 Chapel Hill Consensus Conference...
July 2016: Medicine (Baltimore)
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