scholarly journals Immunoregulation of Neutrophil Extracellular Trap Formation by Endothelial-Derived p33 (gC1q Receptor)

2017 ◽  
Vol 10 (1) ◽  
pp. 30-43 ◽  
Author(s):  
Ariane Neumann ◽  
Praveen Papareddy ◽  
Johannes Westman ◽  
Ole Hyldegaard ◽  
Johanna Snäll ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Enzymatic Activity ◽  
Streptococcus Pyogenes ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Defence Mechanism ◽  
Extracellular Traps ◽  
Molecular Pattern ◽  
Extracellular Trap

The formation of neutrophil extracellular traps (NETs) is a host defence mechanism, known to facilitate the entrapment and growth inhibition of many bacterial pathogens. It has been implicated that the translocation of myeloperoxidase (MPO) from neutrophilic granules to the nucleus is crucial to this process. Under disease conditions, however, excessive NET formation can trigger self-destructive complications by releasing pathologic levels of danger-associated molecular pattern molecules (DAMPs). To counteract such devastating immune reactions, the host has to rely on precautions that help circumvent these deleterious effects. Though the induction of DAMP responses has been intensively studied, the mechanisms that are used by the host to down-regulate them are still not understood. In this study, we show that p33 is an endothelial-derived protein that has the ability to annul NET formation. We found that the expression of human p33 is up-regulated in endothelial cells upon infections with Streptococcus pyogenes bacteria. Using tissue biopsies from a patient with streptococcal necrotising fasciitis, we monitored co-localisation of p33 with MPO. Further in vitro studies revealed that p33 is able to block the formation of DAMP-induced NET formation by inhibiting the enzymatic activity of MPO. Additionally, mice challenged with S. pyogenes bacteria demonstrated diminished MPO activity when treated with p33. Together, our results demonstrate that host-derived p33 has an important immunomodulating function that helps to counterbalance an overwhelming DAMP response.

scholarly journals Neutrophil extracellular traps induce MCP-1 release from endothelial cells at the plaque rupture site in acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Ondracek ◽  
T.M Hofbauer ◽  
A Mangold ◽  
T Scherz ◽  
V Seidl ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endothelial Cells ◽  
Plaque Rupture ◽  
Ex Vivo ◽  
Coronary Intervention ◽  
Neutrophil Extracellular Traps ◽  
Funding Source ◽  
Extracellular Traps

Abstract Introduction Leukocyte-mediated inflammation is crucial in acute myocardial infarction (AMI). We recently observed that neutrophil extracellular traps (NETs) are increased at the culprit site, promoting activation and differentiation of fibrocytes, cells with mesenchymal and leukocytic properties. Fibrocyte migration is mediated by monocyte chemoattractant protein (MCP)-1 and C-C chemokine receptor type 2 (CCR2). We investigated the interplay between NETs, fibrocyte function, and MCP-1 in AMI. Methods Culprit site and femoral blood of AMI patients was drawn during percutaneous coronary intervention. We characterized CCR2 expression of fibrocytes by flow cytometry. MCP-1 and the NET marker citrullinated histone H3 (citH3) were measured by ELISA. Fibrocytes were treated in vitro with MCP-1. Human coronary arterial endothelial cells (hCAECs) were stimulated with isolated NETs, and MCP-1 was measured by ELISA and qPCR. The influence of MCP-1 on NET formation in vitro was assessed using isolated neutrophils. Results We have included 50 consecutive AMI patients into the study. NETs and concentrations of MCP-1 were increased at the CLS. NET stimulation of hCAECs induced MCP-1 on mRNA and protein level. Increasing MCP-1 gradient was associated with fibrocyte accumulation at the site of occlusion. In the presence of higher MCP-1 these fibrocytes expressed proportionally less CCR2 than peripheral fibrocytes. In vitro, MCP-1 dose-dependently decreased fibrocyte CCR2 and reduced ex vivo NET release of healthy donor neutrophils. Conclusions NETs induce endothelial MCP-1 release, presumably promoting a chemotactic gradient for leukocyte and fibrocyte migration. MCP-1 mediated inhibition of NET formation could point to a negative feedback loop. These data will shed light on vascular healing. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund

scholarly journals Differential Use of Human Neutrophil FcγReceptors for Inducing Neutrophil Extracellular Trap Formation

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Omar Rafael Alemán ◽  
Nancy Mora ◽  
Ricarda Cortes-Vieyra ◽  
Eileen Uribe-Querol ◽  
Carlos Rosales
Keyword(s):  
Monoclonal Antibodies ◽  
Human Neutrophil ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Cross Linking ◽  
Erk Activation ◽  
Extracellular Traps ◽  
Extracellular Trap ◽  
Antigen Antibody ◽  
Insight Into

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγreceptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγreceptor is responsible for NET formation, each of the two human Fcγreceptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

scholarly journals Neutrophil extracellular trap formation and nuclease activity in septic patients

2019 ◽  
Author(s):  
Linda Cox ◽  
Kai Walstein ◽  
Lena Völlger ◽  
Friederike Reuner ◽  
Alexandra Bick ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Nuclease Activity ◽  
Positive Control ◽  
Neutrophil Extracellular Trap ◽  
Average Percentage ◽  
Molecular Pattern ◽  
Extracellular Trap ◽  
Net Release

Abstract Background: There is little knowledge, whether in patients with sepsis neutrophil extracellular trap (NET) formation and NET degrading nuclease activity are altered. Thus, we tested the hypotheses that 1) NET formation from neutrophils of septic patients is increased compared to healthy volunteers, both without stimulation and following incubation with mitochondrial DNA (mtDNA), a damage-associated molecular pattern, or phorbol 12-myristate 13-acetate (PMA; positive control); and 2) serum nuclease activities are increased as well. Methods: We included 18 septic patients and 27 volunteers in this prospective observational trial while study was registered retrospectively. Blood was withdrawn and NET formation from neutrophils in vitro was quantified (average percentage of neutrophils showing NET formation on an image) without stimulation and following incubation with mtDNA (10µg/well) or PMA (25nmol). Serum nuclease activity was assessed using gel electrophoresis. Results: In contrast to our hypothesis, compared to healthy volunteers unstimulated NET release from neutrophils in septic patients was decreased by 46.3% (4.3%±1.8 SD vs. 8.2%±2.9, p≤0.0001) and 48.1% (4.9%±2.5 vs. 9.4%±5.2, p=0.002) after 2 and 4 hours of incubation. mtDNA further decreased NET formation in neutrophils from septic patients (4.7%±1.2 to 2.8%±0,8; p=0.03) but did not alter NET formation in neutrophils from volun-teers. As expected, PMA, as positive control, increased NET formation to 73.2% (±29.6) in septic patients and to 91.7% (±7.1) in volunteers after 4 hours of incubation (p=0.22). Serum nuclease activity (range: 0-6) was decreased in septic patients by 39.6% (3±2 vs 5±0; median and ICR, p=0.0001) compared to volunteers. Conclusions: Unstimulated NET formation and nuclease activity are decreased in septic patients and mtDNA can further reduce NET formation. Thus, neutrophils from septic patients show decreased NET formation in vitro despite diminished nuclease activity in vivo. Trail registration DRKS00007694, German Clinical Trials database (DRKS). Registered retrospectively 06.02.2015.

scholarly journals DNase I functional microgels for neutrophil extracellular trap disruption

2021 ◽  
Author(s):  
Aisa Hosseinnejad ◽  
Nadine Ludwig ◽  
Ann-Katrin Wienkamp ◽  
Rahul Rimal ◽  
Christian Bleilevens ◽  
...  
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Dnase I ◽  
Neutrophil Extracellular Trap ◽  
Extracellular Traps ◽  
Extracellular Trap ◽  
Non Fouling

Non-fouling DNase I conjugated microgel provide a novel biohybrid platform to disrupt Neutrophil extracellular traps (NETs) and can be used as a non-thrombogenic coating for reduction of NET-mediated inflammation and microthrombi formation.

scholarly journals The emerging roles of neutrophil extracellular traps in wound healing

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Shuainan Zhu ◽  
Ying Yu ◽  
Yun Ren ◽  
Liying Xu ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Wound Healing Process ◽  
Loss Of Function ◽  
Delayed Wound Healing ◽  
Wound Site ◽  
Extracellular Traps ◽  
Extracellular Trap

AbstractDelayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.

scholarly journals Neutrophil extracellular traps and thrombosis in COVID-19

2020 ◽  
Author(s):  
Yu Zuo ◽  
Melanie Zuo ◽  
Srilakshmi Yalavarthi ◽  
Kelsey Gockman ◽  
Jacqueline A. Madison ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Histone H3 ◽  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Dna Complexes ◽  
Extracellular Traps ◽  
Free Dna ◽  
Extracellular Trap ◽  
Net Release ◽  
D Dimer

ABSTRACTHere, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.

scholarly journals ATP amplifies NADPH-dependent and -independent neutrophil extracellular trap formation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aderonke Sofoluwe ◽  
Marc Bacchetta ◽  
Mehdi Badaoui ◽  
Brenda R. Kwak ◽  
Marc Chanson
Keyword(s):  
Calcium Ionophore ◽  
Neutrophil Extracellular Traps ◽  
Calcium Ionophore A23187 ◽  
Neutrophil Extracellular Trap ◽  
Ionophore A23187 ◽  
Wild Type ◽  
Extracellular Traps ◽  
Brilliant Blue Fcf ◽  
Pathological Conditions

Abstract Neutrophils are the first immune cells to kill invading microbes at sites of infection using a variety of processes, including the release of proteases, phagocytosis and the production of neutrophil extracellular traps (NETs). NET formation, or NETosis, is a specific and highly efficient process, which is induced by a variety of stimuli leading to expulsion of DNA, proteases and antimicrobial peptides to the extracellular space. However, uncontrolled NETosis may lead to adverse effects and exert tissue damage in pathological conditions. Here, we show that the ATP channel pannexin1 (Panx1) is functionally expressed by bone marrow-derived neutrophils (BMDNs) of wild-type (WT) mice and that ATP contributes to NETosis induced in vitro by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate (PMA). Interestingly, neutrophils isolated from Panx1−/− mice showed reduced and/or delayed induction of NETosis. Brilliant blue FCF dye (BB-FCF), a Panx1 channel inhibitor, decreased NETosis in wild-type neutrophils to the extent observed in Panx1−/− neutrophils. Thus, we demonstrate that ATP and Panx1 channels contribute to NETosis and may represent a therapeutic target.

scholarly journals Integrated inertial-impedance cytometry for rapid label-free leukocyte isolation and profiling of neutrophil extracellular traps (NETs)

Lab on a Chip ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 1736-1746 ◽  
Author(s):  
Chayakorn Petchakup ◽  
Hui Min Tay ◽  
King Ho Holden Li ◽  
Han Wei Hou
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Neutrophil Extracellular Trap ◽  
Label Free ◽  
Extracellular Traps ◽  
Trap Formation ◽  
Extracellular Trap ◽  
Impedance Cytometry

A novel integrated inertial-impedance cytometer for rapid and label-free electrical profiling of neutrophil extracellular trap formation (NETosis).

scholarly journals On Neutrophil Extracellular Trap (NET) Removal: What We Know Thus Far and Why So Little

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2079
Author(s):  
Michal Santocki ◽  
Elzbieta Kolaczkowska
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Therapeutic Strategies ◽  
Neutrophil Extracellular Trap ◽  
Know How ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Extracellular Trap

Although neutrophil extracellular traps (NETs) were discovered only 16 years ago, they have already taken us from heaven to hell as we learned that apart from beneficial trapping of pathogens, they cause, or contribute to, numerous disorders. The latter is connected to their persistent presence in the blood or tissue, and we hardly know how they are removed in mild pathophysiological conditions and why their removal is impaired in multiple severe pathological conditions. Herein, we bring together all data available up till now on how NETs are cleared—from engaged cells, their phenotypes, to involved enzymes and molecules. Moreover, we hypothesize on why NET removal is challenged in multiple disorders and propose further directions for studies on NET removal as well as possible therapeutic strategies to have them cleared.

scholarly journals Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2832
Author(s):  
Qian Chen ◽  
Lu Zhang ◽  
Xiang Li ◽  
Wei Zhuo
Keyword(s):  
Tumor Metastasis ◽  
Immune Escape ◽  
Prognostic Biomarker ◽  
Neutrophil Extracellular Traps ◽  
Clinical Applications ◽  
Neutrophil Extracellular Trap ◽  
Pathogenic Microorganisms ◽  
Extracellular Traps ◽  
Extracellular Trap ◽  
Cell Malignancy

Neutrophil extracellular trap (NET) formation is an ability of neutrophils to capture and kill pathogens by releasing chromatin scaffolds, along with associated cytotoxic enzymes and proteases, into the extracellular space. NETs are usually stimulated by pathogenic microorganisms and their products, surgical pressure or hypoxia. Interestingly, a number of recent studies suggest that tumor cells can induce NET formation, which in turn confers tumor cell malignancy. Notably, emerging studies indicate that NETs are involved in enhancing local invasion, increasing vascular permeability and facilitating immune escape and colonization, thus promoting tumor metastasis. In this article, we review the pivotal roles of NETs in the tumor metastasis cascade. We also recapitulate the potential of NETs as a cancer prognostic biomarker and therapeutic target.

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