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https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#1
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29218045/factor-h-c-terminal-domains-are-critical-for-regulation-of-platelet-granulocyte-aggregate-formation
#2
Adam Z Blatt, Gurpanna Saggu, Claudio Cortes, Andrew P Herbert, David Kavanagh, Daniel Ricklin, John D Lambris, Viviana P Ferreira
Platelet/granulocyte aggregates (PGAs) increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP) negative regulator, Factor H (FH). Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS), yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29214674/neutrophil-extracellular-traps-in-plasma-from-dogs-with-immune-mediated-hemolytic-anemia
#3
C Lawson, S A Smith, M O'Brien, M McMichael
BACKGROUND: Neutrophil extracellular traps (NETs) are part of the innate immune response and are essential in local pathogen control, but are associated with pathological inflammation, organ damage, autoimmunity, and thrombosis. Immune-mediated hemolytic anemia (IMHA) is a pro-inflammatory, prothrombotic disease associated with high mortality. HYPOTHESIS/OBJECTIVES: Neutrophil extracellular traps (NETs) are a feature of the inflammatory process in dogs with IMHA...
December 7, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29193703/inflammation-and-thrombosis-roles-of-neutrophils-platelets-and-endothelial-cells-and-their-interactions-in-thrombus-formation-during-sepsis
#4
REVIEW
Toshiaki Iba, Jerrold H Levy
The inflammatory response and the activation of coagulation are two important responses in a host's defense against infection. These mechanisms do not work independently but cooperate in a complex and synchronous manner. Recent research has also shed light on the critical role of thrombus formation that prevents the dissemination of microbes. The cellular components of blood vessels, leukocytes, platelets, erythrocytes, and vascular endothelial cells play significant roles in the development of thrombi in combination with activation of the coagulation system...
November 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29191910/host-dnases-prevent-vascular-occlusion-by-neutrophil-extracellular-traps
#5
Miguel Jiménez-Alcázar, Chandini Rangaswamy, Rachita Panda, Josephine Bitterling, Yashin J Simsek, Andy T Long, Rostyslav Bilyy, Veit Krenn, Christoph Renné, Thomas Renné, Stefan Kluge, Ulf Panzer, Ryushin Mizuta, Hans Georg Mannherz, Daisuke Kitamura, Martin Herrmann, Markus Napirei, Tobias A Fuchs
Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia. In the absence of both DNases, intravascular NETs formed clots that obstructed blood vessels and caused organ damage...
December 1, 2017: Science
https://www.readbyqxmd.com/read/29178989/interaction-of-factor-vii-activating-protease-fsap-with-neutrophil-extracellular-traps-nets
#6
Simona Grasso, Ariane Neumann, Irene M Lang, Michael Etscheid, Maren von Köckritz-Blickwede, Sandip M Kanse
The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP...
November 21, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29178039/platelet-neutrophil-interactions-as-drivers-of-inflammatory-and-thrombotic-disease
#7
REVIEW
Ton Lisman
Neutrophils are well known for their role in infection and inflammatory disease and are first responders at sites of infection or injury. Platelets have an established role in hemostasis and thrombosis and are first responders at sites of vascular damage. However, neutrophils are increasingly recognized for their role in thrombosis, while the immunemodulatory properties of platelets are being increasingly studied. Platelets and neutrophils interact during infection, inflammation and thrombosis and modulate each other's functions...
November 25, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29167411/2-chlorofatty-acids-induce-weibel-palade-body-mobilization
#8
Celine L Hartman, Mark A Duerr, Carolyn J Albert, William L Neumann, Jane McHowat, David A Ford
Endothelial dysfunction is a hallmark of multiple inflammatory diseases. Leukocyte interactions with the endothelium have significant effects on vascular wall biology and pathophysiology. Myeloperoxidase (MPO)-derived oxidant products released from leukocytes are potential mediators of inflammation and endothelial dysfunction. 2-Chlorofatty acids (2-ClFAs) are produced as a result of MPO-derived HOCl targeting plasmalogen phospholipids. Chlorinated lipids have been shown to be associated with multiple inflammatory diseases, but their impact on surrounding endothelial cells has not been examined...
November 22, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29161586/re-cyclin-cell-cycle-components-to-make-nets
#9
Jean Albrengues, Robert W Wysocki, Laura Maiorino, Mikala Egeblad
Neutrophil extracellular traps (NETs) are critical for the clearance of large pathogens and are also implicated in thrombosis, autoimmunity, and cancer. In this issue of Developmental Cell, Amulic et al. (2017) show that the terminally differentiated, non-cycling neutrophils repurpose cell-cycle proteins and pathways to form NETs.
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29156107/hemodynamic-force-triggers-rapid-netosis-within-sterile-thrombotic-occlusions
#10
X Yu, J Tan, S L Diamond
BACKGROUND: Neutrophil extracellular traps (NETs) are released when neutrophils encounter infectious pathogens, especially during sepsis. Additionally, NETosis occurs during venous and arterial thrombosis, disseminated intravascular coagulation, and trauma. OBJECTIVE: We tested if hemodynamic forces trigger NETosis during sterile thrombosis. METHODS: NETs were imaged with Sytox-green during microfluidic perfusion of Factor XIIa-inhibited or thrombin-inhibited human whole blood over fibrillar collagen (± tissue factor)...
November 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29151509/in-paroxysmal-atrial-fibrillation-patients-the-neutrophil-to-lymphocyte-ratio-is-related-to-thrombogenesis-and-more-closely-associated-with-left-atrial-appendage-contraction-than-with-the-left-atrial-body-function
#11
Yukihiro Fukuda, Mitsunori Okamoto, Shunsuke Tomomori, Hiroya Matsumura, Takehito Tokuyama, Yukiko Nakano, Yasuki Kihara
Objective The neutrophil-to-lymphocyte ratio (NLR) is an inflammation marker that can be used to detect atrial inflammatory changes, which may contribute to a reduced left atrial (LA) function and thrombosis. Our study aimed to determine whether or not the association of NLR with the LA appendage (LAA) function in relation to thrombogenesis differs from the association with the LA body function in paroxysmal atrial fibrillation (PAF) patients. Methods A total of 183 PAF patients were studied. The LA volume index, mitral flow velocity (A), and mitral annular motion velocity (A') were examined using transthoracic echocardiography...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29133856/therapeutic-targeting-of-extracellular-dna-improves-the-outcome-of-intestinal-ischemic-reperfusion-injury-in-neonatal-rats
#12
Michael Boettcher, Georg Eschenburg, Stefan Mietzsch, Miguel Jiménez-Alcázar, Michaela Klinke, Deirdre Vincent, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115615/effects-of-dabigatran-regulates-no%C3%A2-reflow-phenomenon-in-acute-myocardial-infarction-mice-through-anti%C3%A2-inflammatory-and-anti%C3%A2-oxidative-activities-and-connective-tissue-growth-factor-expression
#13
Kunqing Song, Yanshan Wang, Jizhang Sheng, Chunmei Ma, Hongmei Li
Pradaxa is a novel oral anticoagulant, which was originally used to prevent thrombosis following joint replacement surgery. The aim of the current study was to investigate the effect dabigatran on acute myocardial infarction through regulating no‑reflow phenomenon and oxidative stress, neutrophil intraplaque infiltration and apoptosis. In the present study, dabigatran significantly inhibited the infarct size, increased arterial pressure and reduced no‑reflow phenomenon in acute myocardial infarction (AMI) vehicle rabbits...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109595/the-role-of-hematological-indices-in-patients-with-acute-coronary-syndrome
#14
REVIEW
Jan Budzianowski, Konrad Pieszko, Paweł Burchardt, Janusz Rzeźniczak, Jarosław Hiczkiewicz
An increased systemic and local inflammation plays a key role in the pathophysiology of acute coronary syndrome (ACS). This review will discuss the role of hematological indices: white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and platelet indices, that is, platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), and platelet distribution width (PDW) in the case of ACS. In recent years, a strong interest has been drawn to these indices, given that they may provide independent information on pathophysiology, risk stratification, and optimal management...
2017: Disease Markers
https://www.readbyqxmd.com/read/29107075/the-role-of-extracellular-histones-in-influenza-virus-pathogenesis
#15
Harshini K Ashar, Nathan C Mueller, Jennifer M Rudd, Timothy A Snider, Mallika Achanta, Maram Prasanthi, Sivasami Pulavendran, Paul G Thomas, Ramachandran Akhilesh, Jerry R Malayer, Jerry W Ritchey, Rachakatla Rajasekhar, Vincent Tk Chow, Charles T Esmon, Narasaraju Teluguakula
Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza...
October 26, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29088921/platelet-to-lymphocyte-ratio-and-neutrophil-to-lymphocyte-ratio-as-risk-factors-for-venous-thrombosis
#16
Andrea Artoni, Maria Abbattista, Paolo Bucciarelli, Francesca Gianniello, Erica Scalambrino, Emanuela Pappalardo, Flora Peyvandi, Ida Martinelli
High platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) are associated with an increased risk of arterial thrombosis, but their role in venous thromboembolism (VTE) has not been fully investigated. A case-control study, of 486 patients with VTE, 100 with cerebral vein thrombosis (CVT), and 299 healthy individuals, was carried out to investigate whether high PLR or NLR values are associated with an increased risk of VTE. Patients with high PLR or NLR did not have an increased risk of VTE (odds ratio [OR] 0...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29052682/probing-blood-cell-mechanics-of-hematologic-processes-at-the-single-micron-level
#17
Jordan C Ciciliano, Reza Abbaspour, Julia Woodall, Caroline Wu, Muhannad S Bakir, Wilbur A Lam
Blood cells circulate in a dynamic fluidic environment, and during hematologic processes such as hemostasis, thrombosis, and inflammation, blood cells interact biophysically with a myriad of vascular matrices-blood clots and the subendothelial matrix. While it is known that adherent cells physiologically respond to the mechanical properties of their underlying matrices, how blood cells interact with their mechanical microenvironment of vascular matrices remains poorly understood. To that end, we developed microfluidic systems that achieve high fidelity, high resolution, single-micron PDMS features that mimic the physical geometries of vascular matrices...
November 7, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29039441/rivaroxaban-attenuates-thrombosis-by-targeting-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-a-rat-model-of-deep-venous-thrombus
#18
Junhao Ma, Xinxi Li, Yang Wang, Zhenwei Yang, Jun Luo
Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis...
September 29, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28962123/whole-genome-gene-expression-changes-and-hematological-effects-of-rikkunshito-in-patients-with-advanced-non-small-cell-lung-cancer-receiving-first-line-chemotherapy
#19
Yung-Che Chen, An-Shen Lin, Yu-Chiang Hung, Kuang-Den Chen, Ching-Yuan Wu, Chien-Hao Lie, Chang-Chun Hsiao, Chung-Jen Chen, Shih-Feng Liu, Wen-Feng Fang, Jen-Chieh Chang, Ting-Ya Wang, Yi-Hsi Wang, Yu-Hsiu Chung, Tung-Ying Chao, Sum-Yee Leung, Mao-Chang Su, Meng-Chih Lin
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28954929/neutrophil-macroaggregates-promote-widespread-pulmonary-thrombosis-after-gut-ischemia
#20
Yuping Yuan, Imala Alwis, Mike C L Wu, Zane Kaplan, Katrina Ashworth, David Bark, Alan Pham, James Mcfadyen, Simone M Schoenwaelder, Emma C Josefsson, Benjamin T Kile, Shaun P Jackson
Gut ischemia is common in critically ill patients, promoting thrombosis and inflammation in distant organs. The mechanisms linking hemodynamic changes in the gut to remote organ thrombosis remain ill-defined. We demonstrate that gut ischemia in the mouse induces a distinct pulmonary thrombotic disorder triggered by neutrophil macroaggregates. These neutrophil aggregates lead to widespread occlusion of pulmonary arteries, veins, and the microvasculature. A similar pulmonary neutrophil-rich thrombotic response occurred in humans with the acute respiratory distress syndrome...
September 27, 2017: Science Translational Medicine
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