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neutrophil, thrombosis

Batric Popovic, Faiez Zannad, Huguette Louis, Isabelle Clerc-Urmès, Cécile Lakomy, Sébastien Gibot, Cécile V Denis, Patrick Lacolley, Véronique Regnault
BACKGROUND: Subjects with heart failure (HF) are at higher risk of developing thrombosis. We investigated whether endothelium activation and inflammation induce a prothrombotic biological profile in patients with acute decompensated HF (ADHF) and sinus rhythm. METHODS: Our prospective study included 34 ADHF patients, 30 patients with stable chronic HF (CHF) and 30 control inpatients without HF. In vitro thrombin generation and its downregulation by activated protein C (APC) was monitored by calibrated automated thrombography at hospital admission, at the day of discharge and after discharge, following at least six weeks of clinical stability...
July 25, 2018: International Journal of Cardiology
Kathryn E Hally, Anne C La Flamme, Scott A Harding, Peter D Larsen
Objectives: Platelets are important regulators of vascular thrombosis and inflammation and are known to express Toll-like receptors (TLRs). Through TLRs, platelets mediate a number of responses by interacting with leucocytes. Here, we report the extent to which platelets modulate in vitro peripheral blood mononuclear cells (PBMCs) and granulocyte responses to TLR4, TLR2/1 and TLR2/6 stimulation in healthy subjects. Methods: Peripheral blood mononuclear cells and granulocytes from 10 healthy volunteers were cultured alone or cocultured with platelets...
2018: Clinical & Translational Immunology
Daigo Nakazawa, Jyaysi Desai, Stefanie Steiger, Susanne Müller, Satish Kumar Devarapu, Shrikant R Mulay, Takamasa Iwakura, Hans-Joachim Anders
Venous thromboembolic (VTE) disease, often manifesting as deep vein thrombosis or pulmonary embolism, involves clot formation consisting of blood cells and platelets locked in plasma protein and chromatin networks. The latter derives from neutrophil extracellular traps released by dying neutrophils; however, the molecular mechanisms of neutrophil death in VTE remains unknown. We speculated that mixed lineage kinase-like (MLKL)-driven neutrophil necroptosis contributes to VTE. Indeed, human inferior venous cava thrombus material stained positive for phosphorylated MLKL, the activated version of MLKL that executes necroptotic cell death...
2018: Cell Death Discovery
Ausra Snipaitiene, Rima Sileikiene, Justina Klimaite, Edita Jasinskiene, Rimantas Uktveris, Lina Jankauskaite
BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory bone disorder that primarily affects young girls, with a mean age of 10 years at onset. Generally, it is a self-limited disease. However, recent data indicate that more than 50% of patients have a chronic persistent disease and about 20% a recurring course of this condition. Also, there are more cases reported with associated auto-inflammatory and autoimmune diseases. In this case report, we present a rare case of sporadic CRMO in which the patient eventually developed C-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies)-associated renal vasculitis and hyperparathyroidism...
July 27, 2018: Pediatric Rheumatology Online Journal
Carsten Deppermann, Paul Kubes
Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation...
July 26, 2018: Innate Immunity
Yacine Boulaftali, Marie-Anne Mawhin, Martine Jandrot-Perrus, Benoît Ho-Tin-Noé
<AbstractText>Glycoprotein VI (GPVI), the main platelet receptor for collagen, has been shown to play a central role in various models of thrombosis, and to be a minor actor of hemostasis at sites of trauma. These observations have made of GPVI a novel target for antithrombotic therapy, as its inhibition would ideally combine efficacy with safety. Nevertheless, recent studies have indicated that GPVI could play an important role in preventing bleeding caused by neutrophils in the inflamed skin and lungs...
April 2018: Research and Practice in Thrombosis and Haemostasis
Alexander Berezin
Diabetes mellitus (DM) is the most important metabolic disease with major threat for public health and increased risk of premature death. The prevalence of DM steadily rises in developing and developed countries achieving the epidemic level. Manifestation and progression of DM corresponds to developing vasculopathies, such as retinopathy, micro- and macro angiopathies, which negatively influence on clinical outcomes and quality-of-life. Although there are remarkable differences in the prevalence of vasculopathy in various types of DM, hyperglycemia and lipotoxicity are discussed as a major factors contributing to vascular complications partly through inducing neutrophil extracellular trap (NET)...
July 17, 2018: Diabetes & Metabolic Syndrome
Eduardo J Folco, Thomas L Mawson, Amélie Vromman, Breno Bernardes-Souza, Grégory Franck, Oscar Persson, Momotaro Nakamura, Gail Newton, Francis W Luscinskas, Peter Libby
OBJECTIVE: Coronary artery thrombosis can occur in the absence of plaque rupture because of superficial erosion. Erosion-prone atheromata associate with more neutrophil extracellular traps (NETs) than lesions with stable or rupture-prone characteristics. The effects of NETs on endothelial cell (EC) inflammatory and thrombogenic properties remain unknown. We hypothesized that NETs alter EC functions related to erosion-associated thrombosis. APPROACH AND RESULTS: Exposure of human ECs to NETs increased VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA and protein expression in a time- and concentration-dependent manner...
July 5, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Mehul R Chorawala, Prem Prakash, Prakash Doddapattar, Manish Jain, Nirav Dhanesha, Anil K Chauhan
BACKGROUND:  Fibronectin splicing variant containing extra domain A (Fn-EDA), which is an endogenous ligand for Toll-like receptor 4 (TLR4), is present in negligible amounts in the plasma of healthy humans, but markedly elevated in patients with co-morbid conditions including diabetes and hyperlipidaemia, which are risk factors for myocardial infarction (MI). Very little is known about the role of Fn-EDA in the pathophysiology of acute MI under these co-morbid conditions. MATERIALS AND METHODS:  We determined the role of Fn-EDA in myocardial ischaemia/reperfusion (I/R) injury in the hyperlipidaemic apolipoprotein E-deficient (ApoE-/- ) mice...
August 2018: Thrombosis and Haemostasis
K Rahman, N Mittal, R Gupta, S Kumar, T Gupta, A Gupta, S Nityanand
INTRODUCTION: There is a paucity of literature related to the prevalence of Paroxysmal Nocturnal haemoglobinuria (PNH) clones in paediatric aplastic anaemia (AA) patients. METHODS: We performed a retrospective analysis over a period of 42 months to study the prevalence of PNH clones in paediatric (age less than 18 years) AA cases, using Fluorescein-labelled proaerolysin-based flow cytometric screening and analysed their clinico-pathological features. RESULTS: PNH clone was identified in 100 (33...
June 25, 2018: International Journal of Laboratory Hematology
Brian A Boone, Pranav Murthy, Jennifer Miller-Ocuin, W Reed Doerfler, Jarrod T Ellis, Xiaoyan Liang, Mark A Ross, Callen T Wallace, Jason L Sperry, Michael T Lotze, Matthew D Neal, Herbert J Zeh
BACKGROUND: The hypercoagulable state associated with pancreatic adenocarcinoma (PDA) results in increased risk of venous thromboembolism, leading to substantial morbidity and mortality. Recently, neutrophil extracellular traps (NETs), whereby activated neutrophils release their intracellular contents containing DNA, histones, tissue factor, high mobility group box 1 (HMGB1) and other components have been implicated in PDA and in cancer-associated thrombosis. METHODS: Utilizing an orthotopic murine PDA model in C57/Bl6 mice and patient correlative samples, we studied the role of NETs in PDA hypercoagulability and targeted this pathway through treatment with the NET inhibitor chloroquine...
June 22, 2018: BMC Cancer
Adi Tabib, Issam Hindi, Netanel Karbian, Orly Zelig, Batla Falach, Dror Mevorach
BACKGROUND: Thrombosis is the prognostic factor with the greatest effect on survival in patients with paroxysmal nocturnal hemoglobinuria (PNH), who lack dozens of membrane surface proteins. We recently described a primary homozygous Cys89Tyr congenital nonfunctioning CD59 in humans with clinical manifestation in infancy, associated with chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy. Here we investigated hypercoagulability mechanisms characterizing the syndrome...
June 11, 2018: Thrombosis Research
Siu Ling Wong, Denisa D Wagner
Peptidylarginine deiminase 4 (PAD4) is a nuclear citrullinating enzyme that is critically involved in the release of decondensed chromatin from neutrophils as neutrophil extracellular traps (NETs). NETs, together with fibrin, are implicated in host defense against pathogens; however, the formation of NETs (NETosis) has injurious effects that may outweigh their protective role. For example, PAD4 activity produces citrullinated neoantigens that promote autoimmune diseases, such as rheumatoid arthritis, to which PAD4 is genetically linked and where NETosis is prominent...
June 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yingjie Han, Frank Y Ma, Julie Di Paolo, David J Nikolic-Paterson
Non-selective inhibitors of spleen tyrosine kinase (SYK) efficiently suppress disease in T cell-dependent models of crescentic glomerulonephritis. However, the therapeutic potential of selective SYK inhibitors in this disease has not been established. In addition, we lack knowledge regarding SYK expression in non-myeloid cells in glomerulonephritis. We addressed these two issues in a rat model of nephrotoxic serum nephritis (NTN) using a SYK inhibitor, GS-492429. Disease was induced in Sprague-Dawley rats (Study 1) or Wistar-Kyoto (WKY) rats (Study 2) by immunization with sheep IgG and administration of sheep anti-rat nephrotoxic serum...
January 2018: International Journal of Immunopathology and Pharmacology
Pavel Poredoš
No abstract text is available yet for this article.
June 2018: VASA. Zeitschrift Für Gefässkrankheiten
Volker Brinkmann
Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled...
June 15, 2018: Journal of Innate Immunity
Junji Moriya
There is accumulating evidence that vascular inflammation plays critical roles in pathophysiology of atherosclerosis. It is widely accepted that both innate and adaptive immune responses are important for initiation and progression of atherosclerosis, which mainly consist of monocytes, macrophages, neutrophils, T lymphocytes, and B lymphocytes. Moreover, inflammatory biomarkers such as high-sensitivity C-reactive protein and interleukin-6 are known to predict future cardiovascular events, as well as conventional low-density or high-density lipoprotein cholesterol...
June 12, 2018: Journal of Cardiology
L L K Leung, J Morser
Two basic carboxypeptidases, carboxypeptidase B2 (CPB2) and carboxypeptidase N (CPN) are present in plasma. CPN is constitutively active, whereas CPB2 circulates as a precursor, procarboxypeptidase B2 (proCPB2), that needs to be activated by the thrombin-thrombomodulin complex or plasmin bound to glycosaminoglycans. The substrate specificities of CPB2 and CPN are similar; they both remove C-terminal basic amino acids from bioactive peptides and proteins, thereby inactivating them. The complement cascade is a cascade of proteases and cofactors activated by pathogens or dead cells, divided into two phases, with the second phase only being triggered if sufficient C3b is present...
June 8, 2018: Journal of Thrombosis and Haemostasis: JTH
Marko Radic, Debendra Pattanaik
The primary anti-phospholipid syndrome (APS) is characterized by the production of antibodies that bind the phospholipid-binding protein β2 glycoprotein I (β2GPI) or that directly recognize negatively charged membrane phospholipids in a manner that may contribute to arterial or venous thrombosis. Clinically, the binding of antibodies to β2GPI could contribute to pathogenesis by formation of immune complexes or modification of coagulation steps that operate along cell surfaces. However, additional events are likely to play a role in pathogenesis, including platelet and endothelial cell activation...
2018: Frontiers in Immunology
Bradley A Herbig, Xinren Yu, Scott L Diamond
Extreme flows can exist within pathological vessel geometries or mechanical assist devices which create complex forces and lead to thrombogenic problems associated with disease. Turbulence and boundary layer separation are difficult to obtain in microfluidics due to the low Reynolds number flow in small channels. However, elongational flows, extreme shear rates and stresses, and stagnation point flows are possible using microfluidics and small perfusion volumes. In this review, a series of microfluidic devices used to study pathological blood flows are described...
July 2018: Biomicrofluidics
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