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neutrophils thrombosis

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https://www.readbyqxmd.com/read/28428204/flow-perturbation-mediates-neutrophil-recruitment-and-potentiates-endothelial-injury-via-tlr2-in-mice-implications-for-superficial-erosion
#1
Grégory Franck, Thomas Mawson, Grasiele Sausen, Manuel Salinas, Gustavo Santos Masson, Andrew P Cole, Marina Beltrami Moreira, Yiannis Chatzizisis, Thibaut Quillard, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Filip K Swirski, Matthias Nahrendorf, Elena Aikawa, Kevin Croce, Peter Libby
Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis...
April 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28408624/activated-protein-c-inhibits-neutrophil-extracellular-trap-formation-in-vitro-and-activation-in-vivo
#2
Laura D Healy, Cristina Puy, José A Fernández, Annachiara Mitrugno, Ravi S Keshari, Nyiawung A Taku, Tiffany T Chu, Xiao Xu, András Gruber, Florea Lupu, John H Griffin, Owen J T McCarty
Activated protein C (APC) is a multi-functional serine protease with anticoagulant, cytoprotective, and anti-inflammatory activities. In addition to the cytoprotective effects of APC on endothelial cells, podocytes, and neurons, APC cleaves and detoxifies extracellular histones, a major component of neutrophil extracellular traps (NETs). NETs promote pathogen clearance but also can lead to thrombosis; the pathways that negatively regulate NETosis are largely unknown. Thus, we studied whether APC is capable of directly inhibiting NETosis via receptor-mediated cell signaling mechanisms...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#3
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28370080/evaluation-of-assays-for-quantification-of-dna-in-canine-plasma-as-an-indirect-marker-of-netosis
#4
Stephanie A Smith, Corinne M Lawson, Maureen A McMichael, Katrina Jung, Mauria O'Brien, Ron Achiel
BACKGROUND: Neutrophil extracellular traps (NET), consisting of a filamentous DNA/chromatin-histone scaffold originating from neutrophils are part of the innate immune response, may be released under a variety of inflammatory conditions and are associated with an increased risk for thrombosis. OBJECTIVES: The purpose of this study was to evaluate a SYTOX green fluorescence assay and a histone-DNA complex (hisDNA) ELISA for quantification of NET-related DNA in canine plasma...
April 3, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28359134/circulating-extracellular-dna-cause-or-consequence-of-thrombosis
#5
Miguel Jiménez-Alcázar, Natalie Kim, Tobias A Fuchs
Thrombosis leads to ischemic organ damage in cardiovascular and thromboembolic diseases. Neutrophils promote thrombosis in vitro and in vivo by releasing neutrophil extracellular traps (NETs). NETs are composed of DNA filaments coated with histones and neutrophil enzymes such as myeloperoxidase (MPO). Circulating extracellular DNA (ceDNA) is widely used as a surrogate marker to monitor NET formation in thrombosis. This narrative review summarizes the association of ceDNA with human thrombosis. Levels of ceDNA indicate the extent and outcome of several cardiovascular and thromboembolic diseases, including myocardial infarction, stroke, and venous thromboembolism...
March 30, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28346125/canine-neutrophil-extracellular-traps-enhance-clot-formation-and-delay-lysis
#6
Unity Jeffery, Dana N LeVine
Autoimmune diseases increase the risk of thrombosis. Neutrophil extracellular traps (NETs) are webs of DNA and protein that may mediate thrombosis in autoimmune diseases. Human and murine studies show NET-releasing neutrophils within a thrombus promote its growth, but it is unclear to what extent NET fragments released into circulation during inflammation are prothrombotic. This study hypothesized that canine NETs promote clot formation and impair lysis even in the absence of neutrophils. NETs were prepared from PMA-stimulated neutrophils and added to fibrinogen and thrombin or to recalcified pooled canine platelet-poor plasma, tissue factor, and tissue plasminogen activator...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28331857/thrombosis-neuroinflammation-and-poststroke-infection-the-multifaceted-role-of-neutrophils-in-stroke
#7
REVIEW
Johanna Ruhnau, Juliane Schulze, Alexander Dressel, Antje Vogelgesang
Immune cells can significantly predict and affect the clinical outcome of stroke. In particular, the neutrophil-to-lymphocyte ratio was shown to predict hemorrhagic transformation and the clinical outcome of stroke; however, the immunological mechanisms underlying these effects are poorly understood. Neutrophils are the first cells to invade injured tissue following focal brain ischemia. In these conditions, their proinflammatory properties enhance tissue damage and may promote ischemic incidences by inducing thrombus formation...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28329607/multiple-mucocutaneous-ulcers-associated-with-cocaine-induced-midline-destructive-lesions
#8
Brittany Blaise, Lucinda Buescher, Morgan L Wilson
Cocaine-induced midline destructive lesions (CIMDL) occur in a small subset of cocaine users, who clinically present with inflammation and necrosis of facial midline structures such as the palate, nasal septum, turbinates, and sinuses. We present a patient with CIMDL occurring concomitantly with ulcers on the cheek and upper trunk. Multiple biopsy specimens from the cutaneous and mucosal lesions consistently showed a dense dermal/submucosal infiltrate of neutrophils and plasma cells, without vasculitis or thrombosis...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28318536/chromobacterium-violaceum-infection-in-a-horse
#9
Márcia Elisa Hammerschmitt, Veronica Machado Rolim, Gustavo Geraldo Medina Snel, Franciele Maboni Siqueira, David Driemeier, Saulo Petinatti Pavarini
Chromobacterium violaceum is an opportunistic pathogen of mammals that produces characteristic violet pigment in bacterial culture. We report pneumonia and septicaemia caused by C. violaceum in a horse. Necropsy examination was performed on a 3-year-old Quarter Horse stallion with a history of recurrent episodes of pneumonia, fever, dyspnoea and sanguineous nasal discharge. The lungs were not collapsed, but they contained dark red foci mixed with white areas, and multiple nodules of firm consistency. Within the liver and kidney there were randomly distributed, multifocal, white pinpoint lesions (0...
March 16, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28303662/mean-platelets-volume-and-neutrophil-to-lymphocyte-ratio-as-predictors-of-stroke
#10
Raymond Farah, Nava Samra
BACKGROUND: Mean platelets volume (MPV) is a marker, which indicates platelet function, and is a potential link between inflammation and thrombosis. Previous studies have found a relation between high MPV levels and high risk of stroke. Another factor that has been associated with the risk of stroke is neutrophil to lymphocyte ratio (NLR). Several studies have reported an association between increased NLR and increased risk of cerebrovascular disease. It was found that NLR levels have a relation to the prognosis as well...
March 17, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28300869/e-selectin-inhibition-with-gmi-1271-decreases-venous-thrombosis-without-profoundly-affecting-tail-vein-bleeding-in-a-mouse-model
#11
Dorian L Culmer, Misha L Dunbar, Angela E Hawley, Suman Sood, Robert E Sigler, Peter K Henke, Thomas W Wakefield, John L Magnani, Daniel D Myers
Selectins, such as E-selectin (CD62E), function in venous thrombosis by binding and activating immune cells to initiate the coagulation cascade. GMI-1271 is a small molecule antagonist that inhibits E-selectin activity. Here we determine whether inhibition of E-selectin is sufficient to decrease acute venous thrombosis and associated inflammatory events in both prophylactic and treatment protocols without significantly affecting haemostasis. Male C57BL/6 mice underwent surgery for experimental thrombosis induction and were harvested at peak thrombus formation in our animal model, two days post induction...
March 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28270931/design-and-methods-of-the-pan-canadian-applying-biomarkers-to-minimize-long-term-effects-of-childhood-adolescent-cancer-treatment-able-nephrotoxicity-study-a-prospective-observational-cohort-study
#12
Kelly R McMahon, Shahrad Rod Rassekh, Kirk R Schultz, Maury Pinsk, Tom Blydt-Hansen, Cherry Mammen, Ross T Tsuyuki, Prasad Devarajan, Geoff D E Cuvelier, Lesley G Mitchell, Sylvain Baruchel, Ana Palijan, Bruce C Carleton, Colin J D Ross, Michael Zappitelli
BACKGROUND: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28245630/structural-basis-of-native-cxcl7-monomer-binding-to-cxcr2-receptor-n-domain-and-glycosaminoglycan-heparin
#13
Aaron J Brown, Krishna Mohan Sepuru, Krishna Rajarathnam
CXCL7, a chemokine highly expressed in platelets, orchestrates neutrophil recruitment during thrombosis and related pathophysiological processes by interacting with CXCR2 receptor and sulfated glycosaminoglycans (GAG). CXCL7 exists as monomers and dimers, and dimerization (~50 μM) and CXCR2 binding (~10 nM) constants indicate that CXCL7 is a potent agonist as a monomer. Currently, nothing is known regarding the structural basis by which receptor and GAG interactions mediate CXCL7 function. Using solution nuclear magnetic resonance (NMR) spectroscopy, we characterized the binding of CXCL7 monomer to the CXCR2 N-terminal domain (CXCR2Nd) that constitutes a critical docking site and to GAG heparin...
February 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28245569/pancreatic-cancer-induced-neutrophil-extracellular-traps-a-potential-contributor-to-cancer-associated-thrombosis
#14
Norbaini Abdol Razak, Omar Elaskalani, Pat Metharom
Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28223279/distinct-contributions-of-complement-factors-to-platelet-activation-and-fibrin-formation-in-venous-thrombus-development
#15
Saravanan Subramaniam, Kerstin Jurk, Lukas Hobohm, Sven Jäckel, Mona Saffarzadeh, Kathrin Schwierczek, Philip Wenzel, Florian Langer, Christoph Reinhardt, Wolfram Ruf
Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity and the coagulation and complement cascades. Here we show in a tissue factor (TF)-dependent model of flow restriction-induced venous thrombosis that complement factors (C) make distinct contributions to platelet activation and fibrin deposition. C3-deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28209798/neutrophil-extracellular-traps-in-atherosclerosis-and-atherothrombosis
#16
REVIEW
Yvonne Döring, Oliver Soehnlein, Christian Weber
Neutrophil extracellular traps expelled from suicidal neutrophils comprise a complex structure of nuclear chromatin and proteins of nuclear, granular, and cytosolic origin. These net-like structures have also been detected in atherosclerotic lesions and arterial thrombi in humans and mice. Functionally, neutrophil extracellular traps have been shown to induce activation of endothelial cells, antigen-presenting cells, and platelets, resulting in a proinflammatory immune response. Overall, this suggests that they are not only present in plaques and thrombi but also they may play a causative role in triggering atherosclerotic plaque formation and arterial thrombosis...
February 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28194438/a-role-for-muscarinic-receptors-in-neutrophil-extracellular-trap-formation-and-levamisole-induced-autoimmunity
#17
Carmelo Carmona-Rivera, Monica M Purmalek, Erica Moore, Meryl Waldman, Peter J Walter, H Martin Garraffo, Karran A Phillips, Kenzie L Preston, Jonathan Graf, Mariana J Kaplan, Peter C Grayson
Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28169486/hepatic-vena-cava-syndrome-new-concept-of-pathogenesis
#18
REVIEW
Santosh Man Shrestha, Masayoshi Kage, Byung Boong Lee
Hepatic vena cava syndrome (HVCS) also known as membranous obstruction of inferior vena cava was considered a rare congenital disease and included under Budd Chiari syndrome. It is now recognized as a bacterial infection induced disease related to poor hygienic living condition. Localized thrombophlebitis of IVC at the site close to hepatic veins (HV) outlets is the initial lesion which converts on resolution into stenosis or complete obstruction, the circulatory equilibrium being maintained by development of cavo-caval collateral anastomosis...
February 7, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28166238/integrin-dependent-cell-adhesion-to-neutrophil-extracellular-traps-through-engagement-of-fibronectin-in-neutrophil-like-cells
#19
Marcello Monti, Francesca Iommelli, Viviana De Rosa, Maria Vincenza Carriero, Roberta Miceli, Rosa Camerlingo, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), originally recognized as a host defense mechanism, were reported to promote thrombosis and metastatic dissemination of cancer cells. Here we tested the role of integrins α5β1 and ανβ3 in the adhesion of cancer cells to NETs. Neutrophil-like cells stimulated with calcium ionophore (A23187) were used as a stable source of cell-free NETs-enriched suspensions. Using NETs as an adhesion substrate, two human K562 cell lines, differentially expressing α5β1 and ανβ3 integrins, were subjected to adhesion assays in the presence or absence of DNAse 1, blocking antibodies against α5β1 or ανβ3, alone or in combination with DNAse 1, and Proteinase K...
2017: PloS One
https://www.readbyqxmd.com/read/28137735/contact-system-activation-and-high-thrombin-generation-in-hyperthyroidism
#20
Namhee Kim, Ja-Yoon Gu, Hyun Ju Yoo, Se Eun Han, Young Il Kim, Il Sung Nam-Goong, Eun Sook Kim, Hyun Kyung Kim
BACKGROUND: Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity. SUBJECTS AND METHODS: In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone-DNA complex, double-stranded DNA and neutrophil elastase) and contact system markers (activated factor XII (XIIa), high-molecular-weight kininogen (HMWK), prekallikrein and bradykinin) were measured...
May 2017: European Journal of Endocrinology
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