Neutrophil extracellular traps

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A scanning electron microscope image of NETs engulfing fungal cells (Candida albicans) in an infected mouse lung. (Click on image for more details.) Neutrophil Extracellular Traps.png
A scanning electron microscope image of NETs engulfing fungal cells ( Candida albicans ) in an infected mouse lung. (Click on image for more details.)
Fluorescent image of cultivated neutrophils isolated from venous blood of human with Alzheimer Disease. Sample was treated with Hoechst 33342 dye that is used to stain DNA. The picture shows the release of DNA by a neutrophil as foggy area in the center of the view field indicating the spontaneous activation of neutrophil extracellular traps (NETs) formation in AD patients that is not usually observed in healthy mates. Magnification x40. Agregation of neutrophils around spontaneously activated netosis observed in Alzheimers' Desease patients blood.jpg
Fluorescent image of cultivated neutrophils isolated from venous blood of human with Alzheimer Disease. Sample was treated with Hoechst 33342 dye that is used to stain DNA. The picture shows the release of DNA by a neutrophil as foggy area in the center of the view field indicating the spontaneous activation of neutrophil extracellular traps (NETs) formation in AD patients that is not usually observed in healthy mates. Magnification x40.

Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. [2] Neutrophils are the immune system's first line of defense against infection and have conventionally been thought to kill invading pathogens through two strategies: engulfment of microbes and secretion of anti-microbials. In 2004, a novel third function was identified: formation of NETs. NETs allow neutrophils to kill extracellular pathogens while minimizing damage to the host cells. [3] Upon in vitro activation with the pharmacological agent phorbol myristate acetate (PMA), Interleukin 8 (IL-8) or lipopolysaccharide (LPS), neutrophils release granule proteins and chromatin to form an extracellular fibril matrix known as NET through an active process. [2]

Contents

Structure and composition

High-resolution scanning electron microscopy has shown that NETs consist of stretches of DNA and globular protein domains with diameters of 15–17 nm and 25 nm, respectively. These aggregate into larger threads with a diameter of 50 nm. [2] However, under flow conditions, NETs can form much larger structures, reaching hundreds of nanometers in length and width. [4]

Analysis by immunofluorescence corroborated that NETs contain proteins from azurophilic granules (neutrophil elastase, cathepsin G and myeloperoxidase), specific granules (lactoferrin), tertiary granules (gelatinase), and the cytoplasm; however, CD63, actin, tubulin and various other cytoplasmatic proteins are not present in NETs. [2] [5]

Anti-microbial activity

NETs disarm pathogens with antimicrobial proteins such as neutrophil elastase, cathepsin G and histones that have a high affinity for DNA. [6] NETs provide for a high local concentration of antimicrobial components and bind, disarm, and kill microbes extracellularly independent of phagocytic uptake. In addition to their antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of the pathogens. Furthermore, delivering the granule proteins into NETs may keep potentially injurious proteins like proteases from diffusing away and inducing damage in tissue adjacent to the site of inflammation. NET formation has also been shown to augment macrophage bactericidal activity in response to multiple bacterial pathogens. [7] [8]

More recently, it has also been shown that not only bacteria but also pathogenic fungi such as Candida albicans induce neutrophils to form NETs that capture and kill C. albicans hyphal as well as yeast-form cells. [9] NETs have also been documented in association with Plasmodium falciparum infections in children. [10]

While it was originally proposed that NETs would be formed in tissues at a site of bacterial/yeast infection, NETs have also been shown to form within blood vessels during sepsis (specifically in the lung capillaries and liver sinusoids). Intra-vascular NET formation is tightly controlled and is regulated by platelets, which sense severe infection via platelet TLR4 and then bind to and activate neutrophils to form NETs. Platelet-induced NET formation occurs very rapidly (in minutes) and may or may not result in death of the neutrophils. [11] NETs formed in blood vessels can catch circulating bacteria as they pass through the vessels. Trapping of bacteria under flow has been imaged directly in flow chambers in vitro and intravital microscopy demonstrated that bacterial trapping occurs in the liver sinusoids and lung capillaries (sites where platelets bind neutrophils). [4]

NETosis

NET activation and release, or NETosis, is a dynamic process that can come in two forms, suicidal and vital NETosis. Overall, many of the key components of the process are similar for both types of NETosis, however, there are key differences in stimuli, timing, and ultimate result. [12]

Activation pathway

The full NETosis activation pathway is still under investigation but a few key proteins have been identified and slowly a full picture of the pathway is emerging. The process is thought to begin with NADPH oxidase activation of protein-arginine deiminase 4 (PAD4) via reactive oxygen species (ROS) intermediaries. PAD4 is responsible for the citrullination of histones in the neutrophil, resulting in decondensation of chromatin. [12] A NADPH oxidase–independent form of NETosis, relying solely on mitochondrial-derived ROS, has also been described. [13] Azurophilic granule proteins such as myeloperoxidase (MPO) and neutrophil elastase (NE) then enter the nucleus and further the decondensation process, resulting in the rupture of the nuclear envelope. The uncondensed chromatin enters the cytoplasm where additional granule and cytoplasmic proteins are added to the early-stage NET. The result of the process then depends on which NETosis pathway is activated. [12]

Suicidal NETosis

Suicidal NETosis was first described in a 2007 study that noted that the release of NETs resulted in neutrophil death through a different pathway than apoptosis or necrosis. [14] In suicidal NETosis, the intracellular NET formation is followed by the rupture of the plasma membrane, releasing it into the extracellular space. This NETosis pathway can be initiated through activation of toll-like receptors (TLRs), Fc receptors, and complement receptors with various ligands such as antibodies, PMA, and so on. [12] [15] The current understanding is that upon activation of these receptors, downstream signaling results in the release of calcium from the endoplasmic reticulum. This intracellular influx of calcium in turn activates NADPH oxidase, resulting in activation of the NETosis pathway as described above. [15] Of note, suicidal NETosis can take hours, even with high levels of PMA stimulation, while vital NETosis can be completed in a matter of minutes. [12]

Vital NETosis

Vital NETosis can be stimulated by bacterial lipopolysaccharide (LPS), other "bacterial products, TLR4-activated platelets, or complement proteins in tandem with TLR2 ligands." [12] Vital NETosis is made possible through the blebbing of the nucleus, resulting in a DNA-filled vesicle that is exocytosed and leaves the plasma membrane intact. [12] Its rapid formation and release does not result in neutrophil death. It has been noted that neutrophils can continue to phagocytose and kill microbes after vital NETosis, highlighting the neutrophil's anti-microbial versatility. [15]

Regulation

The formation of NETs is regulated by the lipoxygenase pathway – during certain forms of activation (including contact with bacteria) neutrophil 5-lipoxygenase forms 5-HETE-phospholipids that inhibit NET formation. [16] Evidence from laboratory experiments suggests that NETs are cleaned away by macrophages that phagocytose and degrade them. [17]

NET-associated host damage

NETs might also have a deleterious effect on the host, because the extracellular exposure of histone complexes could play a role during the development of autoimmune diseases like systemic lupus erythematosus (SLE). [18] NETs could also play a role in inflammatory diseases, as NETs could be identified in preeclampsia, a pregnancy-related inflammatory disorder in which neutrophils are known to be activated. [19] NETs have also been reported in the colon mucosa of patients with the inflammatory bowel disease ulcerative colitis. [20] NETs have also been associated with the production of IgG antinuclear double stranded DNA antibodies in children infected with P. falciparum malaria. [10]

NETs have also been found in cancer patients. [21] Significantly higher levels of NETs have been detected in cancer patients compared to healthy controls, and have been associated with poor prognosis and clinical outcome. [22] Preclinical research suggests that NETs are jointly responsible for cancer-related pathologies like thrombosis, organ failure and metastasis formation. [23] NETs can cause peripheral organ failure or organ dysfunction in cancer patients by obstructing vasculature, causing an inflammatory response, and by releasing cytotoxic components with a direct damaging effect on the tissue. [24]

NETs have been described as potential promoters of metastasis in cancer. They may enhance metastatic spread through various mechanisms. [25] Research has shown that NETs can form in response to infections and surgical stress, which may contribute to metastasis. For instance, A study utilizing the cecal ligation and puncture (CLP) model demonstrated that CLP-induced NETs enhanced the trapping of circulating tumor cells and increased metastasis to the liver. [26] Specifically, when Lewis lung carcinoma cells (LLC-H59) were injected via the intrasplenic route 24 hours after CLP, the mice exhibited a higher number of metastases compared to sham-operated controls. Intravital imaging revealed that NETs colocalized with tumor cells in the liver and lung microvasculature, promoting tumor cell arrest in these areas. [26] NETs can also be induced by cancer cells in the absence of infection or surgical intervention. [25] In a mouse model of breast cancer, it was found that metastatic cancer cells were more effective at inducing NET formation compared to less aggressive cells. [27] Additionally, higher levels of NETs were detected in metastatic lesions of breast cancer patients, particularly in those with triple-negative breast cancer, which is known for its aggressive progression. [27]

NETs have been shown to contribute to the pathogenesis of HIV/SIV. NETs are capable of capturing HIV virions and destroying them. [28] There is an increase in NET production throughout the course of HIV/SIV, which is reduced by ART. In addition, NETs are able to capture and kill various immune cell groups such as CD4+ and CD8+ T cells, B cells, and monocytes. This effect is seen not only with neutrophils in the blood, but also in various tissues such as the gut, lung, liver, and blood vessels. NETs possibly contribute to the hypercoagulable state in HIV by trapping platelets, and expressing tissue factor. [29]

NETs also have a role in thrombosis and have been associated with stroke. [30] [31] [32]

These observations suggest that NETs might play an important role in the pathogenesis of infectious, inflammatory and thrombotic disorders. [33] [34] [35]

Due to the charged and 'sticky' nature of NETs, they may become a problem in cystic fibrosis sufferers, by increasing sputum viscosity. Treatments have focused on breaking down DNA within sputum, which is largely composed of host NET DNA.

A small study published in the journal JAMA Cardiology suggested that NETs played a major role in COVID-19 patients who developed ST-elevation myocardial infarctions. [36]

Related Research Articles

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a blood component whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

<span class="mw-page-title-main">Coagulation</span> Process of formation of blood clots

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.

<span class="mw-page-title-main">Neutrophil</span> Type of white blood cell

Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different animals. They are also known as neutrocytes, heterophils or polymorphonuclear leukocytes.

<span class="mw-page-title-main">Phagocyte</span> Cells that ingest harmful matter within the body

Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.

<span class="mw-page-title-main">Granulocyte</span> Category of white blood cells

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

Granzymes are serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria. Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic granules along with perforin. Granzymes can also be detected in the rough endoplasmic reticulum, golgi complex, and the trans-golgi reticulum. The contents of the cytotoxic granules function to permit entry of the granzymes into the target cell cytosol. The granules are released into an immune synapse formed with a target cell, where perforin mediates the delivery of the granzymes into endosomes in the target cell, and finally into the target cell cytosol. Granzymes are part of the serine esterase family. They are closely related to other immune serine proteases expressed by innate immune cells, such as neutrophil elastase and cathepsin G.

<span class="mw-page-title-main">Myeloperoxidase deficiency</span> Medical condition

Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated.

<span class="mw-page-title-main">Complement component 5a</span> Protein fragment

C5a is a protein fragment released from cleavage of complement component C5 by protease C5-convertase into C5a and C5b fragments. C5b is important in late events of the complement cascade, an orderly series of reactions which coordinates several basic defense mechanisms, including formation of the membrane attack complex (MAC), one of the most basic weapons of the innate immune system, formed as an automatic response to intrusions from foreign particles and microbial invaders. It essentially pokes microscopic pinholes in these foreign objects, causing loss of water and sometimes death. C5a, the other cleavage product of C5, acts as a highly inflammatory peptide, encouraging complement activation, formation of the MAC, attraction of innate immune cells, and histamine release involved in allergic responses. The origin of C5 is in the hepatocyte, but its synthesis can also be found in macrophages, where it may cause local increase of C5a. C5a is a chemotactic agent and an anaphylatoxin; it is essential in the innate immunity but it is also linked with the adaptive immunity. The increased production of C5a is connected with a number of inflammatory diseases.

<span class="mw-page-title-main">P-selectin</span> Type-1 transmembrane protein

P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.

<span class="mw-page-title-main">Platelet factor 4</span> Protein involved in blood clotting, wound healing and inflammation

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 (CXCL4). This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation. It is usually found in a complex with proteoglycan.

<span class="mw-page-title-main">Cathepsin G</span> Protein-coding gene in the species Homo sapiens

Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.

<span class="mw-page-title-main">Degranulation</span> Process by which cells lose secretory granules

Degranulation is a cellular process that releases antimicrobial, cytotoxic, or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulocytes. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms.

<span class="mw-page-title-main">Microvesicle</span> Type of extracellular vesicle

Microvesicles are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.

<span class="mw-page-title-main">S100A9</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A9 (S100A9) also known as migration inhibitory factor-related protein 14 (MRP14) or calgranulin B is a protein that in humans is encoded by the S100A9 gene.

A non-specific immune cell is an immune cell that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. The innate immune system is always present at the site of infection and ready to fight the bacteria; it can also be referred to as the "natural" immune system. The cells of the innate immune system do not have specific responses and respond to each foreign invader using the same mechanism.

Damage-associated molecular patterns (DAMPs) are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen. They are also known as danger signals, and alarmins because they serve as warning signs to alert the organism to any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from mechanical trauma or a pathogen. Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern recognition receptor (PRR). Inflammation is a key aspect of the innate immune response; it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process. As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell which, once released to the extracellular space, binds to the PRR IL-1R, which in turn initiates an inflammatory response to the trauma or pathogen that initiated the release of IL-1α. In contrast to the noninfectious inflammatory response produced by DAMPs, pathogen-associated molecular patterns (PAMPs) initiate and perpetuate the infectious pathogen-induced inflammatory response. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that are released outside the cell following tissue injury. This displacement from the intracellular space to the extracellular space moves the DAMPs from a reducing to an oxidizing environment, causing their functional denaturation, resulting in their loss of function. Outside of the aforementioned nuclear and cytosolic DAMPs, there are other DAMPs originated from different sources, such as mitochondria, granules, the extracellular matrix, the endoplasmic reticulum, and the plasma membrane.

Calprotectin is a complex of the mammalian proteins S100A8 and S100A9. Other names for calprotectin include MRP8-MRP14, calgranulin A and B, cystic fibrosis antigen, L1, 60BB antigen, and 27E10 antigen. The proteins exist as homodimers but preferentially exist as S100A8/A9 heterodimers or heterotetramers (calprotectin) with antimicrobial, proinflammatory and prothrombotic properties. In the presence of calcium, calprotectin is capable of sequestering the transition metals iron, manganese and zinc via chelation. This metal sequestration affords the complex antimicrobial properties. Calprotectin is the only known antimicrobial manganese sequestration protein complex. Calprotectin comprises as much as 60% of the soluble protein content of the cytosol of a neutrophil, and it is secreted by an unknown mechanism during inflammation. Faecal calprotectin has been used to detect intestinal inflammation and can serve as a biomarker for inflammatory bowel diseases. Blood-based calprotectin is used in diagnostics of multiple inflammatory diseases, including autoimmune diseases, like arthritis, and severe infections including sepsis.

Intravascular immunity describes the immune response in the bloodstream, and its role is to fight and prevent the spread of pathogens. Components of intravascular immunity include the cellular immune response and the macromolecules secreted by these cells. It can result in responses such as inflammation and immunothrombosis. Dysregulated intravascular immune response or pathogen evasion can create conditions like thrombosis, sepsis, or disseminated intravascular coagulation.

<span class="mw-page-title-main">Arturo Zychlinsky</span> Biologist

Arturo Zychlinsky is a biologist and since 2001 director at the Max Planck Institute for Infection Biology. His research focuses on Neutrophil Extracellular Traps (NETs) which he discovered together with Volker Brinkmann, and the immune function of chromatin.

References

  1. ↑ Urban, Constantin F.; Ermert, David; Schmid, Monika; Abu-Abed, Ulrike; Goosmann, Christian; Nacken, Wolfgang; Brinkmann, Volker; Jungblut, Peter R.; Zychlinsky, Arturo; Levitz, Stuart M. (30 October 2009). "Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans". PLOS Pathogens. 5 (10): e1000639. doi: 10.1371/journal.ppat.1000639 . PMC   2763347 . PMID   19876394.
  2. 1 2 3 4 Brinkmann, Volker; Ulrike Reichard; Christian Goosmann; Beatrix Fauler; Yvonne Uhlemann; David S. Weiss; Yvette Weinrauch; Arturo Zychlinsky (2004-03-05). "Neutrophil Extracellular Traps Kill Bacteria". Science . 303 (5663): 1532–1535. Bibcode:2004Sci...303.1532B. doi:10.1126/science.1092385. PMID   15001782. S2CID   21628300.
  3. ↑ Nirmala GJ and Lopus M (2020) Cell death mechanisms in eukaryotes. Cell Biol Toxicol, 36, 145–164. doi: /10.1007/s10565-019-09496-2. PMID 31820165
  4. 1 2 Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P (2007). "Platelet Toll-Like Receptor-4 Activates Neutrophil Extracellular Traps to Ensnare Bacteria in Endotoxemic and Septic Blood". Nature Medicine. 13 (4): 463–9. doi:10.1038/nm1565. PMID   17384648. S2CID   22372863.
  5. ↑ Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, Brinkmann V, Jungblut PR, Zychlinsky A (2009). "Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans". PLOS Pathogens. 5 (10): e1000639. doi: 10.1371/journal.ppat.1000639 . PMC   2763347 . PMID   19876394.
  6. ↑ Thomas MP, Whangbo J, McCrossan G, et al. (June 2014). "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". Journal of Immunology. 192 (11): 5390–7. doi:10.4049/jimmunol.1303296. PMC   4041364 . PMID   24771851.
  7. ↑ Monteith, Andrew J.; Miller, Jeanette M.; Maxwell, C. Noel; Chazin, Walter J.; Skaar, Eric P. (September 2021). "Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens". Science Advances. 7 (37): eabj2101. Bibcode:2021SciA....7.2101M. doi: 10.1126/sciadv.abj2101 . PMC   8442908 . PMID   34516771.
  8. ↑ Monteith, Andrew J.; Miller, Jeanette M.; Beavers, William N.; Maloney, K. Nichole; Seifert, Erin L.; Hajnoczky, Gyorgy; Skaar, Eric P. (2021-12-06). "Mitochondrial calcium uniporter affects neutrophil bactericidal activity during Staphylococcus aureus infection". Infection and Immunity. 90 (2): IAI.00551–21. doi:10.1128/IAI.00551-21. ISSN   0019-9567. PMC   8853686 . PMID   34871043. S2CID   244922139.
  9. ↑ Urban, CF; Reichard U; Brinkmann V; Zychlinsky A (April 2006). "Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms". Cellular Microbiology. 8 (4): 668–76. doi: 10.1111/j.1462-5822.2005.00659.x . PMID   16548892.
  10. 1 2 Baker VS, Imade GE, Molta NB, Tawde P, Pam SD, Obadofin MO, Sagay SA, Egah DZ, Iya D, Afolabi BB, Baker M, Ford K, Ford R, Roux KH, Keller TC (February 2008). "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age". Malaria Journal. 7 (41): 41. doi: 10.1186/1475-2875-7-41 . PMC   2275287 . PMID   18312656.
  11. ↑ Caudrillier, Axelle; Kessenbrock, Kai; Gilliss, Brian; Nguyen, John; Marques, Marisa; Monestier, Marc; Toy, Pearl; Werb, Zena; Looney, Mark (2 Jul 2012). "Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury". The Journal of Clinical Investigation. 122 (7): 2661–71. doi:10.1172/JCI61303. PMC   3386815 . PMID   22684106.
  12. 1 2 3 4 5 6 7 Jorch, Selina K.; Kubes, Paul (March 2017). "An emerging role for neutrophil extracellular traps in noninfectious disease". Nature Medicine. 23 (3): 279–287. doi:10.1038/nm.4294. ISSN   1078-8956. PMID   28267716. S2CID   8976515.
  13. ↑ Douda, David Nobuhiro; Khan, Meraj A.; Grasemann, Hartmut; Palaniyar, Nades (2015-03-03). "SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx". Proceedings of the National Academy of Sciences. 112 (9): 2817–2822. Bibcode:2015PNAS..112.2817D. doi: 10.1073/pnas.1414055112 . PMC   4352781 . PMID   25730848.
  14. ↑ Fuchs, Tobias A.; Abed, Ulrike; Goosmann, Christian; Hurwitz, Robert; Schulze, Ilka; Wahn, Volker; Weinrauch, Yvette; Brinkmann, Volker; Zychlinsky, Arturo (2007-01-15). "Novel cell death program leads to neutrophil extracellular traps". The Journal of Cell Biology. 176 (2): 231–241. doi:10.1083/jcb.200606027. ISSN   0021-9525. PMC   2063942 . PMID   17210947.
  15. 1 2 3 Yang, Hang; Biermann, Mona Helena; Brauner, Jan Markus; Liu, Yi; Zhao, Yi; Herrmann, Martin (2016-08-12). "New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation". Frontiers in Immunology. 7: 302. doi: 10.3389/fimmu.2016.00302 . ISSN   1664-3224. PMC   4981595 . PMID   27570525.
  16. ↑ Clark, SR; Guy CJ; Scurr MJ; Taylor PR; Kift-Morgan AP; Hammond VJ; Thomas CP; Coles B; Roberts GW; Eberl M; Jones SA; Topley N; Kotecha S; O'Donnell VB (2011). "Esterified eicosanoids are acutely generated by 5-lipoxygenase in primary human neutrophils and in human and murine infection". Blood. 117 (6): 2033–43. doi:10.1182/blood-2010-04-278887. PMC   3374621 . PMID   21177434.
  17. ↑ Farrera, c; Fadeel B (2013). "Macrophage Clearance of Neutrophil Extracellular Traps Is a Silent Process". Journal of Immunology. 191 (5): 2647–56. doi: 10.4049/jimmunol.1300436 . PMID   23904163.
  18. ↑ Hakkim A, Fürnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V, Herrmann M, Voll RE, Zychlinsky A (2010). "Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis". Proc Natl Acad Sci U S A. 107 (21): 9813–8. Bibcode:2010PNAS..107.9813H. doi: 10.1073/pnas.0909927107 . PMC   2906830 . PMID   20439745.
  19. ↑ Gupta, AK; Hasler P; Holzgreve W; Gebhardt S; Hahn S. (November 2005). "Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia". Hum Immunol. 66 (11): 1146–54. doi:10.1016/j.humimm.2005.11.003. PMID   16571415.
  20. ↑ Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell; Bonderup, Ole Kristian; Glerup, Henning; Bøgsted, Martin; Christiansen, Gunna; Birkelund, Svend; Stensballe, Allan (2015). "Neutrophil Extracellular Traps in Ulcerative Colitis". Inflammatory Bowel Diseases. 21 (9): 2052–2067. doi:10.1097/mib.0000000000000460. PMC   4603666 . PMID   25993694.
  21. ↑ Rayes, Roni F.; Mouhanna, Jack G.; Nicolau, Ioana; Bourdeau, France; Giannias, Betty; Rousseau, Simon; Quail, Daniela; Walsh, Logan; Sangwan, Veena; Bertos, Nicholas; Cools-Lartigue, Jonathan (2019-08-22). "Primary tumors induce neutrophil extracellular traps with targetable metastasis-promoting effects". JCI Insight. 4 (16): e128008. doi:10.1172/jci.insight.128008. ISSN   2379-3708. PMC   6777835 . PMID   31343990.
  22. ↑ Masucci, Maria Teresa; Minopoli, Michele; Del Vecchio, Silvana; Carriero, Maria Vincenza (2020). "The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metastasis". Frontiers in Immunology. 11: 1749. doi: 10.3389/fimmu.2020.01749 . ISSN   1664-3224. PMC   7524869 . PMID   33042107.
  23. ↑ Cedervall, J.; Zhang, Y.; Olsson, A.-K. (2016-08-01). "Tumor-Induced NETosis as a Risk Factor for Metastasis and Organ Failure". Cancer Research. 76 (15): 4311–4315. doi: 10.1158/0008-5472.CAN-15-3051 . ISSN   0008-5472. PMID   27402078.
  24. ↑ Herre, Melanie; Cedervall, Jessica; Mackman, Nigel; Olsson, Anna-Karin (2023-01-01). "Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases". Physiological Reviews. 103 (1): 277–312. doi:10.1152/physrev.00062.2021. ISSN   1522-1210. PMC   9576172 . PMID   35951483.
  25. 1 2 Herre, Melanie; Cedervall, Jessica; Mackman, Nigel; Olsson, Anna-Karin (2023-01-01). "Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases". Physiological Reviews. 103 (1): 277–312. doi:10.1152/physrev.00062.2021. ISSN   0031-9333. PMC   9576172 . PMID   35951483.
  26. 1 2 Cools-Lartigue, Jonathan; Spicer, Jonathan; McDonald, Braedon; Gowing, Stephen; Chow, Simon; Giannias, Betty; Bourdeau, France; Kubes, Paul; Ferri, Lorenzo (2013-08-01). "Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis". Journal of Clinical Investigation. 123 (8): 3446–3458. doi:10.1172/JCI67484. ISSN   0021-9738. PMC   3726160 . PMID   23863628.
  27. 1 2 Bianchini, Giampaolo; Balko, Justin M.; Mayer, Ingrid A.; Sanders, Melinda E.; Gianni, Luca (November 2016). "Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease". Nature Reviews Clinical Oncology. 13 (11): 674–690. doi:10.1038/nrclinonc.2016.66. ISSN   1759-4774. PMC   5461122 . PMID   27184417.
  28. ↑ Saitoh, Tatsuya; Komano, Jun; Saitoh, Yasunori; Misawa, Takuma; Takahama, Michihiro; Kozaki, Tatsuya; Uehata, Takuya; Iwasaki, Hidenori; Omori, Hiroko (July 2012). "Neutrophil Extracellular Traps Mediate a Host Defense Response to Human Immunodeficiency Virus-1". Cell Host & Microbe. 12 (1): 109–116. doi: 10.1016/j.chom.2012.05.015 . ISSN   1931-3128. PMID   22817992.
  29. ↑ Sivanandham, Ranjit; Brocca-Cofano, Egidio; Krampe, Noah; Falwell, Elizabeth; Kilapandal Venkatraman, Sindhuja Murali; Ribeiro, Ruy M.; Apetrei, Cristian; Pandrea, Ivona (2018-09-11). "Neutrophil extracellular trap production contributes to pathogenesis in SIV-infected nonhuman primates". Journal of Clinical Investigation. 128 (11): 5178–5183. doi:10.1172/jci99420. ISSN   1558-8238. PMC   6205390 . PMID   30204591.
  30. ↑ Laridan, Elodie; Denorme, Frederik; Desender, Linda; François, Olivier; Andersson, Tommy; Deckmyn, Hans; Vanhoorelbeke, Karen; De Meyer, Simon F. (August 2, 2017). "Neutrophil extracellular traps in ischemic stroke thrombi". Annals of Neurology. 82 (2): 223–232. doi:10.1002/ana.24993. PMID   28696508. S2CID   205347011.
  31. ↑ Ducroux, Celina; Di Meglio, Lucas; Loyau, Stephane; Delbosc, Sandrine; Boisseau, William; Deschildre, Catherine; Ben Maacha, Malek; Blanc, Raphael; Redjem, Hocine; Ciccio, Gabriele; Smajda, Stanislas; Fahed, Robert; Michel, Jean-Baptiste; Piotin, Michel; Salomon, Laurence; Mazighi, Mikael; Ho-Tin-Noe, Benoit; Desilles, Jean-Philippe (March 2, 2018). "Thrombus Neutrophil Extracellular Traps Content Impair tPA-Induced Thrombolysis in Acute Ischemic Stroke". Stroke. 49 (3): 754–757. doi: 10.1161/STROKEAHA.117.019896 . PMID   29438080.
  32. ↑ Vallés, Juana; Lago, Aída; Santos, María Teresa; Latorre, Ana María; Tembl, José I.; Salom, Juan B.; Nieves, Candela; Moscardó, Antonio (October 5, 2017). "Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance". Thrombosis and Haemostasis. 117 (10): 1919–1929. doi:10.1160/TH17-02-0130. PMID   28837206. S2CID   21968805.
  33. ↑ Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD (Sep 7, 2010). "Extracellular DNA traps promote thrombosis". Proc Natl Acad Sci U S A. 107 (36): 15880–5. Bibcode:2010PNAS..10715880F. doi: 10.1073/pnas.1005743107 . PMC   2936604 . PMID   20798043.
  34. ↑ Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD (Nov 1, 2011). "Neutrophil Extracellular Traps Promote Deep Vein Thrombosis in Mice". Journal of Thrombosis and Haemostasis. 10 (1): 136–144. doi:10.1111/j.1538-7836.2011.04544.x. PMC   3319651 . PMID   22044575.
  35. ↑ Borissoff, JI; ten Cate, H (September 2011). "From neutrophil extracellular traps release to thrombosis: an overshooting host-defense mechanism?". Journal of Thrombosis and Haemostasis. 9 (9): 1791–4. doi: 10.1111/j.1538-7836.2011.04425.x . PMID   21718435. S2CID   5368241.
  36. ↑ Blasco, Ana; Coronado, María-José; Hernández-Terciado, Fernando; Martín, Paloma; Royuela, Ana; Ramil, Elvira; García, Diego; Goicolea, Javier; Del Trigo, María; Ortega, Javier; Escudier, Juan M. (2020-12-29). "Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction". JAMA Cardiology. 6 (4): 469–474. doi: 10.1001/jamacardio.2020.7308 . ISSN   2380-6583. PMC   7772744 . PMID   33372956.
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