Journal of Controlled Release
, Pages 109-119
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Neutrophil extracellular traps (NETs) are structures consisting of decondensed chromatin with associated proteins, including histones and antimicrobial peptides, released from activated neutrophils. They are believed to be one of the body's first lines of defense against infectious agents. Despite their beneficial effect on the immune response process, some studies indicate that their excessive formation and the associated accumulation of extracellular DNA (eDNA) together with other polyelectrolytes (F-actin) plays an important role in the pathogenesis of many diseases. Thus NETs formation and removal are clinically significant. The monoclonal antibody 2C5 has strong specificity for intact nucleohistones (NS) and targets NS in NETs as we previously confirmed. Creation of a nano preparation that can specifically recognize and destroy NETs represents the aim for treatment many diseases. 2C5 antibody functionalized micelles coated with DNase I were created to achieve this aim.
Schematic illustration of the 2C5 targeted MDM (mixed DNase I micelles) components (created by http://Biorender.com).
Neutrophils are the body's first line of defense against pathogens. These cells are produced in the bone marrow and successively released into the circulatory system as fully differentiated neutrophils equipped with numerous granules located in the cytoplasm. Circulating neutrophils can then be recruited to the site of infection or sterile inflammation in response to inflammatory factors . Of the circulating leukocytes, neutrophils are the first to migrate to the site of infection where they initiate active elimination of pathogens, using a wide range of ‘tools’ including phagocytosis, degranulation, and neutrophil extracellular traps (NETs). The role of NETs is to catch, immobilize, facilitate phagocytosis, and in some situations also kill trapped microorganisms . Neutrophilic extracellular networks, originally discovered and described by the team of Arturo Zychlinski from the Max Planck Institute in Berlin (Germany) in 2004, constitute a new, unknown mechanism by which neutrophils can fight pathogens. During this process, activated neutrophils release their DNA in the form of chromatin fibers to which histones and proteins originally found in the granules are present in the neutrophil cytoplasm . Although in their original work on the discovery and characterization of NETs, Arturo Zychlinski's team concluded that ejected neutrophils remain alive, subsequent work by this team reported the death of a neutrophil during this process, which was later termed NETosis (NETosis). However, further studies have shown that NET formation can occur through a rapid ejection of the net by the vesicle system, which does not break the membrane and, consequently, does not cause neutrophil death . This phenomenon was then confirmed by intravital microscopy in studies that showed that after ejection of NETs, neutrophils further phagocytose and migrate towards the bacteria. This type of death was termed “vital NETosis”, contrasted with “lytic NETosis” ending with membrane rupture and neutrophil death . After the initial focus on the undoubtedly positive sides of NET ejection by neutrophils, side effects of their formation began to be noticed over time, including from the participation of the network in many autoimmune diseases, including rheumatoid arthritis (RA) , systemic lupus erythematosus , systemic small vasculitis , as well as in pathologies related to blood clotting  and in the course of sepsis . Moreover, the latest reports indicate that NETs are also involved in the pathogenesis of psoriasis  and coronavirus disease-2019 (COVID19) . Uncontrolled and excessive NET formation within blood vessel provides a coagulation scaffold for red blood cells, platelets, and extracellular vesicles. Therefore, NET formation has been proposed to contribute to thrombus formation in cancer-associated thrombosis . It has been reported that excessive formation of NETs is associated with non-infectious pathological conditions and disposal of the NETs is essential to prevent inadvertent effects.
The innate immune system of the human body has many mechanisms to control the growth and spread of bacteria, including the formation of extracellular neutrophil traps to help prevent bacterial infections. However, microorganisms have developed effective defense systems that not only prevent the formation of NETs or the binding of pathogens in the DNA network, but also prevent the killing of bacteria already bound in anti-bacterial neutrophil traps . Many pathogenic microorganisms use DNases to avoid elimination in NETs. By degrading the DNA strands that make up the core of NETs, the ability of NETs to neutralize pathogens is lost. As in the case of a group Streptococcus bacteria, the secretion of Sda1 DNase has been observed . Similarly, S. pneumoniae endonuclease A (EndA) can degrade extracellular DNA, rendering these bacteria resistant to this bactericidal neutrophil mechanism . Lazzaretto et al. have reported that NETs can be degraded both intracellularly and extracellularly by macrophages and dendritic cells (DCs), respectively. Macrophage-mediated digestion proceeds via TREX1 (DNase III), while the DC-mediated destruction of NETs involves DNase1L3 . Liang et at. have reported the delivery of the staphylococcal nuclease to the intestine to relieve the inflammation in the gut. NETs are involved also in the pathogenesis of several auto-immune diseases, such as type 1 diabetes, and gut immunity plays a key role in its pathogenesis. The use of the staphylococcal nuclease to destroy NETS and alleviate the intestinal inflammatory environment was successful and thereby protects from type 1 diabetes . Recently, it has also been reported that proinflammatory polarization of the macrophages improved their ability to degrade NETs through the improved micropinocytosis. It was reported that increased macrophage content resulted in less NET formed .
When NETs were discovered, it was presumed that NETs are dissolved by DNases since the backbone of NETs is DNA. DNase I is an endonuclease that is present in plasma and digests naked cell-free DNA . It has been therapeutically used to treat NETs that are produced in cystic fibrosis condition , although the systemic application of DNase I that has been shown to have a beneficial effect in many cases [, , , , , ] is non-specific, requires large quantities of the enzyme and can lead to undesirable side-effects including the formation of anti-DNase antibodies. DNase delivery by targeted nanocarriers can solve these issues and allow using DNase. Hosseinnejad, et al. have conjugated DNase I to a microgel as an innovative biohybrid platform to lower the inflammation and microthrombi formation caused by NETs . More controlled release of the DNase I was introduced by Chen J. et al. They developed core–shell nanoparticles consisting of a plasmonic gold blackbody (AuPB) core and a mesoporous polydopamine (mPDA) shell for the delivery of DNase I. The proposed solution triggers release of DNase 1 after photo stimulation with second near-infrared (NIR-II) spectral window . Park, et al. successfully limited DNase short half-life by coating melanin-like nanospheres with polydopamine-immobilized-DNase I to control NET dysregulation in a model of sepsis. The group proved DNase I retained biological activity for 36h and significantly reduced NETosis in a mice model .
The degradation of the DNA in NETs is the final step of targeting NETosis. It has been reported that blocking molecules involved in NETs formation has a therapeutic potential, especially in cancer patients (Fig. 1). Among these molecules are neutrophil elastase (NE) inhibitors, Cl-amidine that blocks PAD4, chloroquine , gasdermin D inhibitors  and disulfiram.
Another option to efficiently deliver active compound into desired part of the body is to use targeted delivery system. Currently, antibodies used to recognize NETs include anti-histone and anti-DNA antibodies as well as antibodies against some other components of NETs, which are not specific enough and cannot differentiate NETs from the products of their degradation [33,34]. Thus, why we propose to use monoclonal antibody with the nucleosome (NS)-restricted specificity - mAb 2C5 recognizes only intact nucleosomes but not their individual components, mixtures of these components, and products of NS degradation [35,36]. mAb 2C5 was shown to effectively recognize various NETs  including compacted NETs and can bring pharmaceutical nanocarriers to NETs and effectively delivers drug-loaded pharmaceutical carriers to NS localization sites, such as tumors.
Due to the pathological aspect of NET formation, it is important to develop an effective pharmacological agent capable of removing these structures. Inspired by the mechanism through which Streptococcus and S. pneumoniaiae destroy NETs and recent findings, we propose mixed micelles that can specifically recognize NETs and promote their degradation due to the combination of specific antibody and DNase I.
Monoclonal antibody mAb 2C5 (Γ2a;κ) was obtained by fusion of myeloma P3X63-Ag8.653 with splenocytes from two non-immunized aged mice (26months-old BALB/c) without overt disease, produced on a commercial basis by Harlan Labs using the 2C5E3 hybridoma cell line from our lab. Horseradish peroxidase anti-DNase I rabbit polyclonal antibodies were purchased from Abcam (ab34592). Hoechst 33342 (H3570) was from Molecular Probes. HL-60 cells and Iscove's Modified Dulbecco's Medium (IMDM) were
DNase conjugate characterization
Gel electrophoresis and Western Blot assay were used as a first method for qualitative analysis of the DNase I-PEG construct. Fig. 3 shows blots stained with anti-DNase I HRP-conjugated antibody. The molecular weight of DNase I was 35kDa. The molecular weight of the conjugate varied depending on how many molecules of pNP-PEG-PE were linked to DNase I as shown in Fig. 2A. There are other bands in addition to 35kDa band in Free DNase I lane, pointing at the existence of the debris of the enzyme
Activation of neutrophils and the consecutive release of NETs was believed to be involved in entrapment, immobilization and killing of the microbes. Recent studies have revealed that NETs play an important role in activation of coagulation and that tissue damage and can be associated with many pathological conditions. Thus, it is imperative to find a treatment methodology to destroy NETs . One of the approaches to destroying NETs involves the dissolution of a basic component of the NET
The mAb2C5 and DNase I constructs, that have the ability to self-organize into micelle-like structure were used as a platform to specifically deliver an enzyme to the NETs. Here, we demonstrated 2C5 MDM nanoparticles that can specifically recognize NETs and promote their degradation. In our studies we applied two different in vitro models of NETosis to confirm the activity of the micelles. In both, applied models we were able to observe NETs formation followed with their degradation after free
CRediT authorship contribution statement
Nina Filipczak: Conceptualization, Methodology, Software, Data curation, Writing – original draft, Visualization, Investigation, Writing – review & editing. Xiang Li: Conceptualization, Methodology, Software, Data curation, Writing – original draft, Visualization, Investigation, Writing – review & editing. Gaurav Rajan Saawant: Methodology, Software, Investigation. Satya Siva Kishan Yalamarty: Methodology, Software, Visualization, Writing – review & editing. Ed Luther: Investigation, Writing –
The authors thank Dr. William C. Hartner for helpful comments and preparation of the manuscript.
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EDTA-mediated inhibition of DNases protects circulating cell-free DNA from ex vivo degradation in blood samples
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In vitro hemolysis: guidance for the pharmaceutical scientist
J. Pharm. Sci.
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Lysis of human red blood cells. 4. Comparison of in vitro and in vivo hemolysis data
J. Pharm. Sci.
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Effect of PEO surface density on long-circulating PLA-PEO nanoparticles which are very low complement activators
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In vitro study of the hemocompatibility of superparamagnetic contrast agent for magnetic resonance imaging
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PEI-based vesicle-polymer hybrid gene delivery system with improved biocompatibility
Int. J. Pharm.
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Nanoparticles for drug delivery in cancer treatment
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p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups
Biochim. Biophys. Acta
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Anti-nuclear autoantibodies of the aged reactive against the surface of tumor but not normal cells
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Ameliorating gut microenvironment through staphylococcal nuclease-mediated intestinal NETs degradation for prevention of type 1 diabetes in NOD mice
An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps
DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps
Neutrophil elastase-deficient mice form neutrophil extracellular traps in an experimental model of deep vein thrombosis
J. Thromb. Haemost.
NETosis: how vital is it?
Neutrophils at work
Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature
Neutrophil extracellular traps kill bacteria
A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus
The multifactorial role of neutrophils in rheumatoid arthritis
Nat. Rev. Rheumatol.
Neutrophil extracellular traps and systemic lupus erythematosus
J. Clin. Cell Immunol.
Netting neutrophils in autoimmune small-vessel vasculitis
Neutrophil extracellular traps induce organ damage during experimental and clinical sepsis
Eosinophils regulate interferon alpha production in plasmacytoid dendritic cells stimulated with components of neutrophil extracellular traps
J. Interf. Cytokine Res.
Neutrophil extracellular traps and by-products play a key role in COVID-19: pathogenesis, risk factors, and therapy
J. Clin. Med.
Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis
Arterioscler. Thromb. Vasc. Biol.
Modulation of neutrophil NETosis: interplay between infectious agents and underlying host physiology
Cited by (1)
Manganese doped nanosystem for degrading neutrophil extracellular traps and improving chemotherapy efficiency to synergistically inhibit lung metastasis of breast cancer
2023, Chemical Engineering Journal
New treatment patterns have emerged by destroying neutrophil extracellular traps (NETs) with DNase-1 to prevent tumor metastasis. However, the DNase-1 as a therapeutic agent has short half-life in blood plasma and low potency to kill tumor owing to the intrinsically intricate tumor microenvironment. Herein, a manganese-enriched nanosystem (DMMnSiO3-PEG/DOX/DNase-1) has been developed to inhibit lung metastasis of breast cancer by delivering doxorubicin and DNase-1 for degrading neutrophil extracellular traps and improving chemotherapy therapy synergistically. Specifically, this PEG-modified nanosystem can not only accumulate at the site of tumor tissue but also be captured by NETs. In tumor site, DOX were released from this nanosystem in response to a lower pH and higher GSH to facilitate apoptosis effect of tumor cells efficiently with the help of DNase-1. Then, those remaining nanoparticles were captured by NETs to disassemble them and the released Mn2+ as the cofactor of DNase-1 could increase the NETs lyse. In all, that nanosystem has been proven to inhibit tumor growth by a chemotherapeutic effect and suppresses distant metastasis by disassembling NETs through in vitro and in vivo evaluations. This strategy demonstrates immense potential to provide an effective and safe therapeutic regimen for the treatment in patients with metastatic breast cancer.
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What do neutrophil extracellular traps NETs do? ›
These structures, called neutrophil extracellular traps (NETs), represent an important strategy to immobilize and kill invading microorganisms. The NET scaffold consists of chromatin fibers with a diameter of 15–17 nm; DNA and histones represent the major NET constituents (2).How do you detect neutrophil extracellular traps? ›
Sytox green assay
A standard, well-accepted method of NET detection directly from neutrophils is the staining of extracellular DNA with Sytox Green (29–33). This technique is also used to assess NETs in patient plasma/serum yet is not specific for NETosis alone.
Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms.What are the neutrophil extracellular traps NETs made out of? ›
Neutrophil extracellular traps (NETs) are made of a network of extracellular strings of DNA that bind pathogenic microbes. Histones and several neutrophil granule proteins associated with the DNA framework damage entrapped microorganisms.What are neutrophil extracellular traps in sepsis? ›
Similarly, neutrophil extracellular traps (NETs) are released from neutrophils during inflammation. NETs are webs of extracellular DNA decorated with histones, myeloperoxidase, and elastase. Although NETs contribute to pathogen clearance, excessive NET formation promotes inflammation and tissue damage in sepsis.What is neutrophil extracellular traps in the autoimmunity context? ›
Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis.How is neutrophilia diagnosed? ›
Other tests that can help diagnose neutrophilia once CBC and peripheral blood smear have been reviewed are bone marrow biopsy, flow cytometry, and molecular/genetic testing. Bone marrow biopsy helps establish the diagnosis of various hematological and non-hematological malignancies invading bone marrow.How do you detect NETs? ›
A biopsy is the removal of a small amount of tissue for examination under a microscope and is required to make a diagnosis of NET. A pathologist then analyzes the sample(s) removed during the biopsy.What inflammation causes high neutrophils? ›
Secondary neutrophilia causes are linked to various infections, inflammation caused by medical conditions and your body's reaction to stress. Secondary causes include: Infection and inflammation. Acute chronic inflammation that's caused by rheumatoid arthritis and inflammatory bowel disease.What infection causes neutrophils? ›
Acute bacterial infections, such as pneumococcal, staphylococcal, or leptospiral infections, are the most frequent causes of infection-induced neutrophilia. Certain viral infections, such as herpes complex, varicella, and EBV infections, may also cause neutrophilia.
What infections are associated with neutrophils? ›
Neutrophilia can result from acute infections caused by any of the following pathogens: Cocci (eg, staphylococci, pneumococci, streptococci, meningococci, gonococci) Bacilli (eg, Escherichia coli, Pseudomonas aeruginosa, Actinomyces species) Certain fungi (eg, Coccidioides immitis, Candida albicans)What are NETs in bacterial infection? ›
Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins.How are neutrophil extracellular traps NETs formed? ›
Neutrophil extracellular traps (NETs) are formed as a defense mechanism to immobilize invading microorganisms but also in response to sterile triggers. NETs consist of a DNA scaffold decorated with granule-derived proteins, such as enzymatically active proteases and anti-microbial peptides.What triggers net formation? ›
Formation of NETs can be activated by various pathogens, such as bacteria, fungi, protozoa, viruses, as well as bacterial cell wall components – lipopolysaccharides (LPS).Do high neutrophils indicate sepsis? ›
As mentioned above, neutrophils are involved in the process of sepsis, and a relative increase in the total number of circulating neutrophils or an increase in the percentage of immature forms is also closely related to sepsis.How do I know if I have neutropenic sepsis? ›
The signs and symptoms of neutropenic sepsis can be unclear and patients may not have many symptoms. If a patient has neutropenia or is having chemotherapy or other immunosuppressant therapy, look out for: reports of feeling generally unwell. flu-like symptoms.What organism is most likely to cause neutropenic sepsis? ›
Neutropenic sepsis is commonly caused by bacterial infection with Gram-positive pathogens such as Staphylococcus aureus, Enterococcus sp, Streptococcus pneumoniae and S.Are neutrophils high in autoimmune disease? ›
Neutrophils are an essential part of your immune system. They destroy harmful bodily invaders that cause infections, like fungi and bacteria. With autoimmune neutropenia, your immune system mistakenly attacks these white blood cells. As a result, you have a lower-than-normal level of neutrophils in your blood.What is autoimmune disorder neutrophils? ›
As effector cells, neutrophils promote autoimmune disease by releasing cytokines and chemokines cascades that accompany inflammation, neutrophil extracellular traps (NETs) regulating immune responses through cell–cell interactions.What antibodies are in autoimmune neutropenia? ›
Autoimmune neutropenia of infancy (AIN), also called primary autoimmune neutropenia, is a disease in which antibodies recognize membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb receptor), causing their peripheral destruction.
What cancers are high in neutrophils? ›
Neutrophils can also influence the migration potential of cancer cells. In several types of cancer it has been shown that neutrophils promote metastasis. These tumors include skin squamous cell carcinoma , melanoma , adenocarcinomas , HNSCC , and breast cancer .How serious is neutrophilia? ›
Severely high or low levels of white blood cells often require emergency care and monitoring. People with severe neutropenia will have inadequate defense against infection. People with severe neutrophilia typically have a life threatening infection or other inflammatory illness that requires treatment, such as cancer.Do high neutrophils mean inflammation? ›
Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage by macrophages. These actions are orchestrated by numerous cytokines and the expression of their receptors, which represent a potential means for inhibiting selective aspects of inflammation.What infections cause low neutrophils? ›
Infections: Viral, bacterial and parasitic infections can cause neutropenia. Common causes include HIV, hepatitis, tuberculosis, sepsis, and Lyme disease, among other infections.What cancers cause neutropenia? ›
Causes of neutropenia
Cancers that affect the bone marrow directly, such as leukemia, lymphoma, and multiple myeloma. Cancer that has spread. Radiation therapy to several parts of the body or to bones in the pelvis, legs, chest, or abdomen.
Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring.What are NETs in autoimmune diseases? ›
NETs can promote the production of ACPAs, release immune stimulatory molecules such as IL-6 and IL-8, and stimulate autoimmune responses. In turn, ACPAs can also stimulate the production of NETs, thus forming a vicious cycle. NETs levels in RA patients were positively correlated with ACPAs levels (22, 58).What is the marker for neuroendocrine tumors? ›
5-HIAA (5-hydroxyindoleacetic acid) is a substance made from serotonin and measured in the urine. High levels may mean symptoms are caused by carcinoid syndrome or carcinoid crisis. 5-HIAA is usually the first biochemical marker checked when a person has symptoms of carcinoid syndrome.How long can you live with a neuroendocrine tumor? ›
If the tumor has spread to nearby tissue or the regional lymph nodes, the 5-year relative survival rate is 96%. If the tumor has spread to distant areas of the body, the relative 5-year survival rate is 68%.What drugs cause high neutrophils? ›
GCSFs, such as Neupogen (filgrastim, Amgen), Granix (tbo-filgrastim, Cephalon, Inc.), and Zarxio (filgrastim-sndz, Sandoz), stimulate and promote the maturation and activation of neutrophils. This class of drugs can also enhance the exodus of mature neutrophils trapped within the bone marrow.
What infections cause high WBC and neutrophils? ›
Disorders related to having a high white blood count include: Autoimmune and inflammatory diseases, conditions that cause the immune system to attack healthy tissues. Bacterial or viral infections. Cancers such as leukemia and Hodgkin disease.Does COVID cause high neutrophils? ›
Severe disease in COVID-19 is associated to increased neutrophil-to-lymphocyte ratio and high expression of neutrophil-related cytokines IL-8 and IL-6 in serum, and neutrophilia has been described as a predictor of poor outcome (4–14).What attracts neutrophils to an infected area? ›
Neutrophils are the first cells to reach the site of infection, attracted by chemotactic factors such as complement, with their predominant role being phagocytosis.Which bacterial infection is most common in neutropenia? ›
Bacterial bloodstream infections (BSIs) rank first in terms of infectious complications during neutropenia and the inadequacy of the inflammatory response makes sepsis a significant cause of death in this setting.How do NETs cause inflammation? ›
NETs may play significant roles in the initiation phase of autoimmune disorders by exposing intracellular endogenous components to the immune system, which exacerbates inflammation or even results in the production of autoantibodies.Are NETs inflammatory? ›
Components of NETS are non-specific, and other than controlling microbes, they cause injury to surrounding tissue by themselves or by increasing the pro-inflammatory response.What are NETs in lupus? ›
NETs have a dual function of maintaining hematologic homeostasis and of defending the organism. They are released not only on exposure to pathogens such as bacteria, but also in sterile environments in autoimmune diseases such as lupus where they generate/trap autoantigens and aggravate inflammation.How do neutrophils trap bacteria? ›
Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria.How are NETs cleared? ›
How NETs are cleared is incompletely understood. Human macrophages can engulf NETs through endocytosis without inducing cytokine secretion. Conversely, impaired NET clearance by macrophages is associated with sustained inflammation, for example, as reported in ARDS.How do neutrophils trap pathogens? ›
Another mechanism that neutrophils employ against pathogens is phagocytosis; a neutrophil is recruited by chemotaxis, followed by the recognition of antigens on the pathogen surface, and finally the uptake of the foreign pathogen, which is mediated by oxygen-dependent or -independent pathways .
What is neutrophil degranulation? ›
The process by which neutrophils mobilize granules is called degranulation. Degranulation can occur at the plasma membrane for extracellular release (killing extracellular microorganisms) or to the phagosome for intracellular delivery (killing intracellular microorganisms) .What are a few of the major pathologies that NETs have been implicated in? ›
In addition to their role in defense against microbes, NETs have been implicated as mediators of pathology in sterile inflammation, such as cancer and autoimmunity, and their potential as therapeutic targets is actively explored.What is the extracellular trap formation? ›
Extracellular trap formation (ETosis) by various blood cells has been reported. This trap contains DNA, histones and granular proteins which can elicit an innate immune response by entrapping microorganisms. The trap thus formed has been reported to have an involvement in various pathogenic conditions as well.What is the potential role of neutrophil extracellular traps in cardio oncology? ›
Neutrophil extracellular traps (NETs)—entities with released DNA, proteases, proinflammatory and prooxidative substances from blasted neutrophils—play an important role in cancer proliferation, propagation metastasis, and incident CV events (acute coronary syndrome, thromboembolic events, and heart failure).What is the function of NETosis? ›
NETosis includes release of the granule components into the cytosol, modification of histones leading to chromatin decondensation, destruction of the nuclear envelope, as well as formation of pores in the plasma membrane.What is the role of NETosis? ›
NETosis provides a mechanism for stimulation of autoimmunity as the nuclear DNA, histones, and granule proteins released by the NETs serve as self-antigens. Hakkim et al. found that in a subset of patients with SLE, degradation of NETs was lessened compared to a pool of healthy, unrelated blood donors .How does NETosis control infection? ›
Among their weaponry, they have the ability to mix and extrude their DNA and bactericidal molecules creating NET-like structures in a unique type of cell death called NETosis. This process is important in order to control extracellular infections limiting collateral damage.How do neutrophils promote tumors? ›
Neutrophils promote tumor cell survival and extravasation at sites of metastatic dissemination, and, in particular, CD11b(+)/Ly6G(+) neutrophils enhance metastasis by inhibiting functions of NK cells, so significantly increasing the intraluminal tumor cell survival.What is the role of neutrophils in leukemia? ›
Chronic Neutrophilic Leukemia (CNL)
In CNL, these changes affect the normal growth and development of a type of white blood cell called a “neutrophil.” Neutrophils travel to the site of an infection. They fight the infection by ingesting microorganisms and releasing enzymes that kill the microorganisms.
Half of people with cancer who are receiving chemotherapy have some level of neutropenia. It is a common side effect in people with leukemia. People who have neutropenia have a higher risk of getting serious infections. This is because they do not have enough neutrophils to kill organisms that cause infection.
Does NETosis cause inflammation? ›
There is a possible production of autoantibodies against nucleic acids released by neutrophils undergoing NETosis [19, 68] with the generated immune complexes representing a source of self-antigens that enhance the autoimmune and inflammatory process. This in turn results in more injury and inflammation [20, 69].What is net in inflammation? ›
NETs under physiological conditions are central to pathogen clearance. When there is excessive formation or suboptimal, NETs are able to initiate further destructive signalling through interaction with other tissue constituents and the immune system.What is the function of neutrophils inflammation? ›
Neutrophils dominate the early stages of inflammation and set the stage for repair of tissue damage by macrophages. These actions are orchestrated by numerous cytokines and the expression of their receptors, which represent a potential means for inhibiting selective aspects of inflammation.Why is NETosis bad? ›
Under normal circumstances, NETosis is a self-defense strategy. Nonetheless, the formation of NETs can become se a pathogenic stimulus in many diseases such as cancer, autoimmune diseases (e.g. rheumatoid arthritis), lung diseases, atherosclerosis, venous thromboembolic diseases, and COVID-19.Are neutrophils involved in chronic inflammation? ›
Neutrophils are normally the first responders to acute inflammation and contribute to the resolution of inflammation. However, in chronic inflammation, the role of neutrophils is less well understood and has been described as either beneficial or detrimental, causing tissue damage and enhancing the immune response.What type of infection does neutrophils fight off? ›
Neutrophils recognize viruses and virus‐infected cells and infiltrate into the sites of infection. At the onset of a viral infection, neutrophils are rapidly recruited at the site of infection from the blood and are mobilized to differentiate and migrate out of the bone marrow.