scholarly journals Endocytosis of soluble immune complexes leads to their clearance by FcγRIIIB but induces neutrophil extracellular traps via FcγRIIA in vivo

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4421-4431 ◽  
Author(s):  
Kan Chen ◽  
Hiroshi Nishi ◽  
Richard Travers ◽  
Naotake Tsuboi ◽  
Kimberly Martinod ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Fluid Phase ◽  
Neutrophil Extracellular Traps ◽  
Humoral Factors ◽  
Extracellular Traps ◽  
Fluid Phase Endocytosis ◽  
Soluble Immune Complexes ◽  
The Individual

Abstract Soluble immune complexes (ICs) are abundant in autoimmune diseases, yet neutrophil responses to these soluble humoral factors remain uncharacterized. Moreover, the individual role of the uniquely human FcγRIIA and glycophosphatidylinositol (GPI)–linked FcγRIIIB in IC-mediated inflammation is still debated. Here we exploited mice and cell lines expressing these human neutrophil FcγRs to demonstrate that FcγRIIIB alone, in the absence of its known signaling partners FcγRIIA and the integrin Mac-1, internalizes soluble ICs through a mechanism used by GPI-anchored receptors and fluid-phase endocytosis. FcγRIIA also uses this pathway. As shown by intravital microscopy, FcγRIIA but not FcγRIIIB-mediated neutrophil interactions with extravascular soluble ICs results in the formation of neutrophil extracellular traps (NETs) in tissues. Unexpectedly, in wild-type mice, IC-induced NETosis does not rely on the NADPH oxidase, myeloperoxidase, or neutrophil elastase. In the context of soluble ICs present primarily within vessels, FcγRIIIB-mediated neutrophil recruitment requires Mac-1 and is associated with the removal of intravascular IC deposits. Collectively, our studies assign a new role for FcγRIIIB in the removal of soluble ICs within the vasculature that may serve to maintain homeostasis, whereas FcγRIIA engagement of tissue soluble ICs generates NETs, a proinflammatory process linked to autoimmunity.

scholarly journals The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Vital Role ◽  
Extracellular Traps ◽  
Protein Components ◽  
Cancer Associated Thrombosis ◽  
Coagulation Pathway

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

scholarly journals Recent advances in pathophysiology of disseminated intravascular coagulation: the role of circulating histones and neutrophil extracellular traps

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2143 ◽  
Author(s):  
Yasir Alhamdi ◽  
Cheng-Hock Toh
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Cell Injury ◽  
Neutrophil Extracellular Traps ◽  
Intravascular Coagulation ◽  
Extracellular Traps ◽  
Complex Interactions ◽  
Recent Advances ◽  
Novel Biomarkers

Disseminated intravascular coagulation (DIC) is an acquired condition that develops as a complication of systemic and sustained cell injury in conditions such as sepsis and trauma. It represents major dysregulation and increased thrombin generationin vivo. A poor understanding and recognition of the complex interactions in the coagulation, fibrinolytic, inflammatory, and innate immune pathways have resulted in continued poor management and high mortality rates in DIC. This review focuses attention on significant recent advances in our understanding of DIC pathophysiology. In particular, circulating histones and neutrophil extracellular traps fulfil established criteria in DIC pathogenesis. Both are damaging to the vasculature and highly relevant to the cross talk between coagulation and inflammation processes, which can culminate in adverse clinical outcomes. These molecules have a strong potential to be novel biomarkers and therapeutic targets in DIC, which is still considered synonymous with ‘death is coming’.

scholarly journals Immunomodulatory Role of Clarithromycin in Acinetobacter baumannii Infection via Formation of Neutrophil Extracellular Traps

2015 ◽  
Vol 60 (2) ◽  
pp. 1040-1048 ◽  
Author(s):  
Theocharis Konstantinidis ◽  
Konstantinos Kambas ◽  
Alexandros Mitsios ◽  
Maria Panopoulou ◽  
Victoria Tsironidou ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Ex Vivo ◽  
Neutrophil Extracellular Traps ◽  
Macrolide Antibiotics ◽  
Dependent Manner ◽  
Biofilm Inhibition ◽  
Content Type ◽  
Extracellular Traps

ABSTRACTMacrolide antibiotics have been shown to act as immunomodulatory molecules in various immune cells. However, their effect on neutrophils has not been extensively investigated. In this study, we investigated the role of macrolide antibiotics in the generation of neutrophil extracellular traps (NETs). By assessingex vivoandin vivoNET formation, we demonstrated that clarithromycin is able to induce NET generation bothin vitroandin vivo. Clarithromycin utilizes autophagy in order to form NETs, and these NETs are decorated with antimicrobial peptide LL-37. Clarithromycin-induced NETs are able to inhibitAcinetobacter baumanniigrowth and biofilm formation in an LL-37-dependent manner. Additionally, LL-37 antimicrobial function depends on NET scaffold integrity. Collectively, these data expand the knowledge on the immunomodulatory role of macrolide antibiotics via the generation of LL-37-bearing NETs, which demonstrate LL-37-dependent antimicrobial activity and biofilm inhibition againstA. baumannii.

scholarly journals Role of neutrophil extracellular traps in radiation resistance of invasive bladder cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Surashri Shinde-Jadhav ◽  
Jose Joao Mansure ◽  
Roni F. Rayes ◽  
Gautier Marcq ◽  
Mina Ayoub ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Potential Therapeutic Target ◽  
Extracellular Traps ◽  
Tumor Immune Microenvironment

AbstractRadiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.

scholarly journals In Vivo Imaging of Neutrophil Extracellular Traps (NETs): Visualization Methods and Outcomes

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Sultan Z. Alasmari
Keyword(s):  
Neutrophil Extracellular Traps ◽  
Immune Defense ◽  
Innate Immune ◽  
First Line ◽  
The Third ◽  
Extracellular Traps ◽  
Host Pathogen Interaction ◽  
Unique Method

Neutrophils comprise the first line of innate immune defense during a host-pathogen interaction. They attack microorganisms directly through three different methods, of which, phagocytosis and degranulation have been known and well-studied for decades. The formation of neutrophil extracellular traps (NETs) is the third and unique method, which was unveiled in 2004. Since then, many studies on NETs have been carried out. However, only few have successfully demonstrated the activity of NETs in vivo. Results of the in vivo studies on NETs have strengthened our understanding of their role in different situations. This review highlights the main in vivo studies, which have contributed in extending our understanding of the role of NETs during infections and diseases, thus indicating their advantages and limitations.

scholarly journals In Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody-Mediated Venous Thrombosis

2017 ◽  
Vol 69 (3) ◽  
pp. 655-667 ◽  
Author(s):  
He Meng ◽  
Srilakshmi Yalavarthi ◽  
Yogendra Kanthi ◽  
Levi F. Mazza ◽  
Megan A. Elfline ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Neutrophil Extracellular Traps ◽  
Antiphospholipid Antibody ◽  
Extracellular Traps

scholarly journals Neutrophil Extracellular Traps Facilitate Sympathoexcitation After Traumatic Brain Injury Via HMGB1/AP1 Signaling Pathway

2021 ◽  
Author(s):  
Kaixin Zhu ◽  
Xiaoxiang Hou ◽  
Xiaolin Qu ◽  
Wen Chen ◽  
Kun Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Diffuse Axonal Injury ◽  
Neutrophil Extracellular Traps ◽  
Control Group ◽  
Extracellular Traps ◽  
Important Form

Abstract Background: Traumatic brain injury (TBI) usually accompanies with sympathetic excitation, and paradoxical sympathetic hyperactivity (PSH) may be detrimental to the prognosis of TBI sufferers. Neutrophils can form neutrophil extracellular traps (NETs) to get involved in the neuroinflammation after TBI. As an important form of NETs, HMGB1 were found to activate the expression of AP1, which can increase the formation of IL-1β in microglia. Considering that IL-1β is able to regulate sympathoexcitation, it is reasonable to infer that HMGB1/AP1 signaling plays an important role in sympathoexcitation after TBI. Methods: In this present study, rat model with diffuse axonal injury (DAI) was established. The existance of NETs and the expression level of HMGB1/AP1/IL-1β in the paraventricular nucleus (PVN) after DAI were examined by immunofluorescence and Western blot (WB). The role of HMGB1/AP1 in the activation of microglia, secretion of IL-1β and sympathoexcitaiton were identified in vitro. Moreover, stereotaxic injection of anti-HMGB1 or HMGB1 was conducted to further validate the effect of HMGB1/AP1 pathway on sympathoexcitation after TBI.Results: The indicators of sympathoexcitation, including mean arterial pressure and serum catecholamine, increased and peaked at 72 hours after TBI. The formation of NETs was observed in PVN after injury, whereas, no NETs were found in the control group. And meanwhile, levels of NETs in PVN were higher than that in the para-PVN tissues after the injury. In vitro experiments showed that HMGB1 can promote the activation of microglia as well as increase the expression of AP1 and IL-1β. In vivo experiments suggested HMGB1 have an impact on the expression of AP1 and IL-1β in the PVN, and further controlling the sympathoexcitation after TBI.Conclusion: NETs might mediate sympathoexcitation after TBI through microglial activation in the PVN in a HMGB1/AP1/IL-1β dependent way.

scholarly journals Neutrophil extracellular traps are present in the airways of ENaC-overexpressing mice with cystic fibrosis-like lung disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samantha L. Tucker ◽  
Demba Sarr ◽  
Balázs Rada
Keyword(s):  
Cystic Fibrosis ◽  
Flow Cytometry ◽  
Bacterial Infections ◽  
Lavage Fluid ◽  
Neutrophil Extracellular Traps ◽  
Lung Damage ◽  
Specific Marker ◽  
Extracellular Traps

Abstract Background Neutrophils are key components of the exacerbated inflammation and tissue damage in cystic fibrosis (CF) airways. Neutrophil extracellular traps (NETs) trap and kill extracellular pathogens. While NETs are abundant in the airways of CF patients and have been hypothesized to contribute to lung damage in CF, the in vivo role of NETs remains controversial, partially due to lack of appropriate animal models. The goal of this study was to detect NETs and to further characterize neutrophil-mediated inflammation in the airways of mice overexpressing the epithelial sodium channel (βENaC-Tg mice on C57BL/6 background) in their lung with CF-like airway disease, in the absence of any apparent bacterial infections. Methods Histology scoring of lung tissues, flow cytometry, multiplex ELISA, immunohistochemistry and immunofluorescence were used to characterize NETs and the airway environment in uninfected, βENaC-Tg mice at 6 and 8 weeks of age, the most chronic time points so far studied in this model. Results Excessive neutrophilic infiltration characterized the lungs of uninfected, βENaC-Tg mice at 6 and 8 weeks of age. The bronchoalveolar lavage fluid (BALF) of βENaC-Tg mice contains increased levels of CF-associated cytokines and chemokines: KC, MIP-1α/β, MCP-1, G-CSF, IL-5, and IL-6. The BALF of βENaC-Tg mice contain MPO-DNA complexes, indicative of the presence of NETs. Immunofluorescence and flow cytometry of BALF neutrophils and lung tissues demonstrated increased histone citrullination, a NET-specific marker, in βENaC-Tg mice. Conclusions NETs are detected in the airways of βENaC-Tg mice, in the absence of bacterial infections. These data demonstrate the usefulness of the βENaC-Tg mouse to serve as a model for studying the role of NETs in chronic CF airway inflammation.

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