Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps

2014 ◽  
Vol 12 (12) ◽  
pp. 2074-2088 ◽  
Author(s):  
N. Maugeri ◽  
L. Campana ◽  
M. Gavina ◽  
C. Covino ◽  
M. De Metrio ◽  
...  
Keyword(s):  
High Mobility ◽  
Neutrophil Extracellular Traps ◽  
High Mobility Group ◽  
Extracellular Traps ◽  
Activated Platelets

scholarly journals Activated platelets induce MLKL-driven neutrophil necroptosis and release of neutrophil extracellular traps in venous thrombosis

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Daigo Nakazawa ◽  
Jyaysi Desai ◽  
Stefanie Steiger ◽  
Susanne Müller ◽  
Satish Kumar Devarapu ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Activated Platelets

scholarly journals Endocarditis Pathogen Promotes Vegetation Formation by Inducing Intravascular Neutrophil Extracellular Traps Through Activated Platelets

Circulation ◽  
2015 ◽  
Vol 131 (6) ◽  
pp. 571-581 ◽  
Author(s):  
Chiau-Jing Jung ◽  
Chiou-Yueh Yeh ◽  
Ron-Bin Hsu ◽  
Chii-Ming Lee ◽  
Chia-Tung Shun ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Activated Platelets ◽  
Vegetation Formation

scholarly journals Neutrophil extracellular traps promote scar formation in post-epidural fibrosis

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Zhen Jin ◽  
Jinpeng Sun ◽  
Zeyuan Song ◽  
Kun Chen ◽  
Yap San Min Nicolas ◽  
...  
Keyword(s):  
High Mobility ◽  
Major Complication ◽  
Neutrophil Extracellular Traps ◽  
Scar Formation ◽  
Degraded Dna ◽  
Epidural Fibrosis ◽  
Wound Area ◽  
Extracellular Traps ◽  
Shed Light

Abstract Low back pain following spine surgery is a major complication due to excessive epidural fibrosis, which compresses the lumbar nerve. The mechanisms of epidural fibrosis remain largely elusive. In the drainage samples from patients after spine operation, neutrophil extracellular traps (NETs) and NETs inducer high-mobility group box 1 were significantly increased. In a mouse model of laminectomy, NETs developed in the wound area post epidural operation, accompanied with macrophage infiltration. In vitro, macrophages ingested NETs and thereby increased the elastase from NETs via the receptor for advanced glycation end product. Moreover, NETs boosted the expression of fibronectin in macrophages, which was dependent on elastase and could be partially blocked by DNase. NF-κB p65 and Smad pathways contributed to the increased expression fibronectin in NETs-treated macrophages. In the mouse spine operation model, post-epidural fibrosis was significantly mitigated with the administration of DNase I, which degraded DNA and cleaved NETs. Our study shed light on the roles and mechanisms of NETs in the scar formation post spine operation.

scholarly journals Targeting myeloid-cell specific integrin α9β1 inhibits arterial thrombosis in mice

Blood ◽  
2020 ◽  
Vol 135 (11) ◽  
pp. 857-861 ◽  
Author(s):  
Nirav Dhanesha ◽  
Manasa K. Nayak ◽  
Prakash Doddapattar ◽  
Manish Jain ◽  
Gagan D. Flora ◽  
...  
Keyword(s):  
Arterial Thrombosis ◽  
Potential Role ◽  
Myeloid Cell ◽  
Neutrophil Extracellular Traps ◽  
Cathepsin G ◽  
Wild Type ◽  
Extracellular Traps ◽  
Laser Injury ◽  
Activated Platelets

Abstract Evidence suggests that neutrophils contribute to thrombosis via several mechanisms, including neutrophil extracellular traps (NETs) formation. Integrin α9β1 is highly expressed on neutrophils when compared with monocytes. It undergoes affinity upregulation on neutrophil activation, and stabilizes adhesion to the activated endothelium. The role of integrin α9 in arterial thrombosis remains unexplored. We generated novel myeloid cell-specific integrin α9−/− mice (α9fl/flLysMCre+) to study the role of integrin α9 in arterial thrombosis. α9fl/fl littermates were used as controls. We report that α9fl/flLysMCre+ mice were less susceptible to arterial thrombosis in ferric chloride (FeCl3) and laser injury-induced thrombosis models with unaltered hemostasis. Neutrophil elastase-positive cells were significantly reduced in α9fl/flLysMCre+ mice concomitant with reduction in neutrophil count, myeloperoxidase levels, and red blood cells in the FeCl3 injury-induced carotid thrombus. The percentage of cells releasing NETs was significantly reduced in α9fl/flLysMCre+ mouse neutrophils stimulated with thrombin-activated platelets. Furthermore, we found a significant decrease in neutrophil-mediated platelet aggregation and cathepsin-G secretion in α9fl/flLysMCre+ mice. Transfusion of α9fl/fl neutrophils in α9fl/flLysMCre+ mice restored thrombosis similar to α9fl/fl mice. Treatment of wild-type mice with anti-integrin α9 antibody inhibited arterial thrombosis. This study identifies the potential role of integrin α9 in modulating arterial thrombosis.

Neutrophil extracellular traps are a source of extracellular HMGB1 in lupus nephritis: associations with clinical and histopathological features

Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1549-1557 ◽  
Author(s):  
L P Whittall-García ◽  
J Torres-Ruiz ◽  
A Zentella-Dehesa ◽  
M Tapia-Rodríguez ◽  
J Alcocer-Varela ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
High Mobility ◽  
Disease Activity Index ◽  
Neutrophil Extracellular Traps ◽  
Hmgb1 Protein ◽  
Sledai Score ◽  
Histopathological Features ◽  
Extracellular Traps

Objective This study aimed to analyze the expression of the high mobility group box-1 (HMGB1) protein in neutrophil extracellular traps (NETs) of patients with lupus nephritis (LN) and its association with clinical and histopathological features of the disease. Methods Twenty-three patients with biopsy-confirmed LN and 14 systemic lupus erythematosus (SLE) patients with active disease (SLE Disease Activity Index (SLEDAI) score ≥ 6) and no evidence of LN were included. Clinical and laboratory features were recorded. NETs and the expression of HMGB1 were assessed by confocal microscopy, and serum HMGB1 levels were measured by ELISA. Results In comparison to patients without kidney disease, patients with LN had a higher expression of HMGB1 in spontaneous (57 vs. 30.4; p = 0.027) and lipopolysaccharide (LPS)-induced (55.8 vs. 24.9; p = 0.005) NETs. We found a positive correlation between serum HMGB1 and the expression of HMGB1 in LPS-induced NETs ( r = 0.447, p = 0.017). The expression of HMGB1 in spontaneous NETs correlated with SLEDAI score ( r = 0.514, p = 0.001), anti-dsDNA antibodies ( r = 0.467, p = 0.004), the rate of glomerular filtration descent ( r = 0.543, p = 0.001), and diverse histopathological components of active nephritis in the kidney biopsy, such as the activity index ( r = 0.581, p = 0.004), fibrinoid necrosis ( r = 0.603, p = 0.002), and cellular crescents ( r = 0.486, p = 0.019). Conclusions In patients with SLE, NETs are a source of extracellular HMGB1. The expression of HMGB1 in NETs is higher among patients with LN, which correlates with clinical and histopathological features of active nephritis and suggest a possible role of this alarmin in the pathophysiology of kidney damage in SLE.

Platelets Induce Neutrophil Extracellular Traps in Transfusion-Related Acute Lung Injury

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-18-SCI-18 ◽  
Author(s):  
Mark R. Looney
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Platelet Activation ◽  
Conflicts Of Interest ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Activated Platelets ◽  
Extracellular Histones ◽  
Cellular Mediators ◽  
Injury Models

Abstract Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality in the U.S. and a major cause of transfusion-associated morbidity including increased time on mechanical ventilation and length of stay in the intensive care unit and the hospital. Neutrophils have been identified as critical cellular mediators in the pathogenesis of TRALI in both clinical studies and in experimental settings using a variety of injury models. Platelets have been implicated as a blood product that can trigger TRALI, and endogenous platelet activation contributes to lung injury. Platelets bind to the surface of neutrophils to form heterotypic aggregates, and activated platelets can trigger the formation of neutrophil extracellular traps (NETs), which is a new mode of neutrophil death that is distinct from apoptosis and necrosis. NETs are produced in experimental TRALI and are increased in post-transfusion plasma from patients who develop TRALI. Blocking platelet activation reduces the production of NETs and lung injury, and inhibiting NETs by blocking extracellular histones or dismantling the NET structure with DNase1 are strongly protective in TRALI. In conclusion, TRALI is an immune-mediated event in which activated platelets, neutrophils, and NETs, contribute to injury and are therefore targets for therapeutic intervention. Disclosures No relevant conflicts of interest to declare.

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