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https://www.readbyqxmd.com/read/29929138/prothrombotic-mechanisms-in-patients-with-congenital-p-cys89tyr-mutation-in-cd59
#1
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
https://www.readbyqxmd.com/read/29924943/peptidylarginine-deiminase-4-a-nuclear-button-triggering-neutrophil-extracellular-traps-in-inflammatory-diseases-and-aging
#2
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
https://www.readbyqxmd.com/read/29923438/an-inhibitor-of-spleen-tyrosine-kinase-suppresses-experimental-crescentic-glomerulonephritis
#3
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
https://www.readbyqxmd.com/read/29912675/insufficient-evidence-to-conclude-that-neutrophil-to-lymphocyte-ratio-predicts-deep-venous-thrombosis
#4
Pavel Poredoš
No abstract text is available yet for this article.
June 2018: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/29909412/neutrophil-extracellular-traps-in-the-second-decade
#5
REVIEW
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
https://www.readbyqxmd.com/read/29907363/critical-roles-of-inflammation-in-atherosclerosis
#6
REVIEW
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
https://www.readbyqxmd.com/read/29883024/carboxypeptidase-b2-and-carboxypeptidase-n-in-the-cross-talk-between-coagulation-thrombosis-inflammation-and-innate-immunity
#7
REVIEW
L L K Leung, J Morser
Two basic carboxypeptidases, carboxypeptidase B2 (CPB2) and carboxypeptidase N (CPN) are present in plasma. CPN is constitutively active, while 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 specificity of CPB2 and CPN are similar, removing 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 triggered if sufficient C3b is present...
June 8, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29867951/cellular-and-molecular-mechanisms-of-anti-phospholipid-syndrome
#8
REVIEW
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
https://www.readbyqxmd.com/read/29861812/using-microfluidic-devices-to-study-thrombosis-in-pathological-blood-flows
#9
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
https://www.readbyqxmd.com/read/29848170/relative-deficiency-of-plasma-adamts13-activity-and-elevation-of-human-neutrophil-peptides-in-patients-with-traumatic-brain-injury
#10
Monisha A Kumar, Wenjing Cao, Huy P Pham, Dheeraj Raju, Kelsey Nawalinski, Eileen Maloney Wilensky, James M Schuster, X Long Zheng
Traumatic microvascular injury (tMVI) is a universal endophenotype of traumatic brain injury (TBI) that is responsible for significant neurological morbidity and mortality. The mechanism underlying tMVI is not fully understood. The present study aims to determine plasma levels of von Willebrand factor (VWF), a disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS)-13 activity, and human neutrophil peptides (HNP) 1-3 and to correlate these biomarkers with functional outcomes following moderate-severe TBI...
May 31, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29843771/neutrophil-extracellular-traps-induce-aggregation-of-washed-human-platelets-independently-of-extracellular-dna-and-histones
#11
Omar Elaskalani, Norbaini Binti Abdol Razak, Pat Metharom
BACKGROUND: The release of neutrophil extracellular traps (NETs), a mesh of DNA, histones and neutrophil proteases from neutrophils, was first demonstrated as a host defence against pathogens. Recently it became clear that NETs are also released in pathological conditions. NETs released in the blood can activate thrombosis and initiate a cascade of platelet responses. However, it is not well understood if these responses are mediated through direct or indirect interactions. We investigated whether cell-free NETs can induce aggregation of washed human platelets in vitro and the contribution of NET-derived extracellular DNA and histones to platelet activation response...
May 29, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29797525/four-cases-of-acute-infectious-urticaria-showing-significant-elevation-of-plasma-d-dimer-level
#12
Toshifumi Takahashi, Shino Minami, Kazuya Teramura, Toshihiro Tanaka, Noriki Fujimoto
D-dimer, a fibrinolytic end-product, has been regarded as a biomarker indicating the severity of urticaria, especially in chronic urticaria. Regarding acute urticaria, D-dimer level is also suggested to be elevated, which may be significant in comparison with chronic urticaria. However, the clinical features of acute urticaria with concomitant significant elevation of D-dimer level have not been investigated in detail so far. We present four cases of acute urticaria fulfilling the proposed diagnostic criterion of acute infectious urticaria, in which significant elevation of D-dimer level and rapid spontaneous normalization in parallel with the resolution of fever and urticaria occurs...
May 24, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29716535/predictive-value-of-neutrophil-to-lymphocyte-ratio-in-patients-with-acute-st-segment-elevation-myocardial-infarction-after-percutaneous-coronary-intervention-a-meta-analysis
#13
Sai Zhang, Jun Diao, Chunmei Qi, Jingjing Jin, Li Li, Xingjuan Gao, Lei Gong, Weiheng Wu
BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is an indicator of systemic inflammation and a prognostic marker in patients with acute coronary syndrome (ACS). This study aims to investigate the value of NLR to predict the in-hospital and long-term prognosis in patients with ST segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) by meta-analysis. METHOD: The studies related to the prognosis of NLR and STEMI patients published in the Pubmed, Embase, and Ovid databases before June 2017 were retrieved...
May 2, 2018: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29703474/platelets-nets-and-cancer
#14
Jessica Cedervall, Anahita Hamidi, Anna-Karin Olsson
In addition to the central role of platelets in hemostasis, they contribute to pathological conditions such as inflammation and tumor progression. Aberrant expression and/or exposure of pro-coagulant factors in the tumor microenvironment induce platelet activation and subsequent release of growth factors from platelet granules. Cancer patients are commonly affected by thrombotic events, as a result of tumor-induced platelet activation. A novel player potentially contributing to cancer-associated thrombosis is the formation of neutrophil extracellular traps (NETs)...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29670076/cathelicidins-prime-platelets-to-mediate-arterial-thrombosis-and-tissue-inflammation
#15
Joachim Pircher, Thomas Czermak, Andreas Ehrlich, Clemens Eberle, Erik Gaitzsch, Andreas Margraf, Jochen Grommes, Prakash Saha, Anna Titova, Hellen Ishikawa-Ankerhold, Konstantin Stark, Tobias Petzold, Thomas Stocker, Ludwig T Weckbach, Julia Novotny, Markus Sperandio, Bernhard Nieswandt, Alberto Smith, Hanna Mannell, Barbara Walzog, David Horst, Oliver Soehnlein, Steffen Massberg, Christian Schulz
Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29643232/increased-neutrophil-extracellular-trap-formation-promotes-thrombosis-in-myeloproliferative-neoplasms
#16
Ofir Wolach, Rob S Sellar, Kimberly Martinod, Deya Cherpokova, Marie McConkey, Ryan J Chappell, Alexander J Silver, Dylan Adams, Cecilia A Castellano, Rebekka K Schneider, Robert F Padera, Daniel J DeAngelo, Martha Wadleigh, David P Steensma, Ilene Galinsky, Richard M Stone, Giulio Genovese, Steven A McCarroll, Bozenna Iliadou, Christina Hultman, Donna Neuberg, Ann Mullally, Denisa D Wagner, Benjamin L Ebert
Thrombosis is a major cause of morbidity and mortality in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), clonal disorders of hematopoiesis characterized by activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. Neutrophil extracellular trap (NET) formation, a component of innate immunity, has been linked to thrombosis. We demonstrate that neutrophils from patients with MPNs are primed for NET formation, an effect blunted by pharmacological inhibition of JAK signaling...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29609040/clinico-hematological-profile-and-thrombotic-hemorrhagic-events-in-150-chinese-patients-with-essential-thrombocythemia
#17
Dian Zhou, Wei Chen, Hai Cheng, Jian-Lin Qiao, Li-Li Zhu, Zhen-Yu Li, Kai-Lin Xu
Essential thrombocythemia (ET) is an uncommon chronic myeloproliferative disorder with no cure. Patients with ET are at risk of different complications, and currently there are no optimal prognostic standards to predict severe post-diagnosis complications such as thrombosis and hemorrhage. In this study, we retrospectively analyzed the full set of clinical data from 150 Chinese patients with ET enrolled from 2013 to 2016. We discovered that neutrophil-to-lymphocyte ratio (NLR), along with other known clinical parameters such as age, leukocyte count, incidence of thrombotic events is higher in patients with JAK2 V617F mutation...
March 27, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29608758/neutrophil-extracellular-trap-release-is-associated-with-antinuclear-antibodies-in-systemic-lupus-erythematosus-and-anti-phospholipid-syndrome
#18
Maarten van der Linden, Lucas L van den Hoogen, Geertje H A Westerlaken, Ruth D E Fritsch-Stork, Joël A G van Roon, Timothy R D J Radstake, Linde Meyaard
Objectives: Increased release of neutrophil extracellular traps (NETs) is implicated in the activation of plasmacytoid dendritic cells, vascular disease and thrombosis in SLE and APS. However, studies comparing NET release between patients with SLE and APS are lacking. Here we evaluated plasma-induced NET release in a large cohort of patients with SLE, SLE + APS and primary APS in relation to clinical and serological parameters. Methods: Neutrophils from healthy controls were exposed to plasma of heterologous healthy controls (n = 27) or SLE (n = 55), SLE + APS (n = 38) or primary APS (PAPS) (n = 28) patients and NET release was quantified by immunofluorescence...
March 28, 2018: Rheumatology
https://www.readbyqxmd.com/read/29584534/the-pro-inflammatory-role-of-platelets-in-cancer
#19
A K Olsson, J Cedervall
Thrombosis is a frequent issue in cancer patients. Tumor-induced platelet activation and coagulation does not only constitute a significant risk for thrombosis, but also contribute to tumor progression by promoting critical processes such as angiogenesis and metastasis. In addition to their role in hemostasis, platelets are increasingly recognized as regulators of inflammation. By modulating the immune system, platelets regulate several aspects of cancer-associated pathology. Platelets influence the inflammatory response in cancer by affecting the activation status of the endothelium and by recruiting leukocytes to primary and metastatic tumor sites, as well as to distant organs unaffected by tumor growth...
March 27, 2018: Platelets
https://www.readbyqxmd.com/read/29572206/roles-of-pad4-and-netosis-in-experimental-atherosclerosis-and-arterial-injury-implications-for-superficial-erosion
#20
Grégory Franck, Thomas L Mawson, Eduardo J Folco, Roberto Molinaro, Victoria Ruvkun, Daniel Engelbertsen, Xin Liu, Yevgenia Tesmenitsky, Eugenia Shvartz, Galina K Sukhova, Jean-Baptiste Michel, Antonino Nicoletti, Andrew H Lichtman, Denisa D Wagner, Kevin J Croce, Peter Libby
<u>Rationale:</u> Neutrophils likely contribute to the thrombotic complications of human atheromata. In particular, neutrophil extracellular traps (NETs) could exacerbate local inflammation and amplify and propagate arterial intimal injury and thrombosis. Peptidyl arginine deiminase 4 (PAD4) participates in NET formation, but understanding of this enzyme's role in atherothrombosis remains scant. <u>Objective:</u> This study tested the hypothesis that PAD4 and NETs influence experimental atherogenesis and in processes implicated in superficial erosion, a form of plaque complication we previously associated with NETs...
March 23, 2018: Circulation Research
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