Neutrophil extracellular traps and their role in the development of chronic inflammation and autoimmunity (original) (raw)
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Neutrophil extracellular Traps and its implications in inflammation: An Overview
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin. Several proteins adhere to NETs, including histones and over 30 components of primary and secondary granules, among them components with bactericidal activity such as elastase, myeloperoxidase, cathepsin G, lactoferrin, pentraxin 3, gelatinase, proteinase 3, LL37, peptidoglycan-binding proteins, and others with bactericidal activity able to destroy virulence factors. Three models for NETosis are known to date. (a) Suicidal NETosis, with a duration of 2-4 h, is the best described model. (b) In vital NETosis with nuclear DNA release, neutrophils release NETs without exhibiting loss of nuclear or plasma membrane within 5-60 min, and it is independent of reactive oxygen species (ROS) and the Raf/MERK/ERK pathway. (c) The final type is vital NETosis with release of mitochondrial DNA that is dependent on ROS and produced after stimuli with GM-CSF and lipopolysaccharide. Recent research has revealed neutrophils as more sophisticated immune cells that are able to precisely regulate their granular enzymes release by ion fluxes and can release immunomodulatory cytokines and chemokines that interact with various components of the immune system. Therefore, they can play a key role in autoimmunity and in autoinflammatory and metabolic diseases. In this review, we intend to show the two roles played by neutrophils: as a first line of defense against microorganisms and as a contributor to the pathogenesis of various illnesses, such as autoimmune, autoinflammatory, and metabolic diseases.
Neutrophil extracellular traps and their role in health and disease
The human innate immune system is indispensable for protection against potentially invasive microbial and viral pathogens, either neutralising them or containing their spread until effective mobilisation of the slower, adaptive (specific), immune response. Until fairly recently, it was believed that the human innate immune system possessed minimal discriminatory activity in the setting of a rather limited range of microbicidal or virucidal mechanisms. However, recent discoveries have revealed that the innate immune system possesses an array of novel pathogen recognition mechanisms, as well as a resourceful and effective alternative mechanism of phagocyte (predominantly neutrophil)-mediated, anti-infective activity known as NETosis. The process of NETosis involves an unusual type of programmed, purposeful cell death, resulting in the extracellular release of a web of chromatin heavily impregnated with antimicrobial proteins. These structures, known as neutrophil extracellular traps (NETs), immobilise and contribute to the eradication of microbial pathogens, ensuring that the anti-infective potential of neutrophils is sustained beyond the lifespan of these cells. The current review is focused on the mechanisms of NETosis and the role of this process in host defence. Other topics reviewed include the potential threats to human health posed by poorly controlled, excessive formation of NETs, specifically in relation to development of autoimmune and cardiovascular diseases, as well as exacerbation of acute and chronic inflammatory disorders of the airways.
Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation
International Journal of Nanomedicine
Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones and antimicrobial proteins. As a key mechanism for neutrophils to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, and viruses). Although NETs are mostly known for mediating microbial killing, increasing evidence suggests that excessive NETs induced by stimulation of physical and chemical components, microorganisms, and pathological factors can exacerbate inflammation and organ damage. This review summarizes the induction and role of NETs in inflammation and focuses on the strategies of inhibiting NETosis and the mechanisms involved in pathogen evasion of NETs. Furthermore, herbal medicine inhibitors and nanodelivery strategies improve the efficiency of inhibition of excessive levels of NETs.
Neutrophil Extracellular Traps in the Second Decade
Journal of Innate Immunity, 2018
Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled. This review provides a concise overview on the far-reaching functions of NETs in health and disease.
Frontiers in Immunology, 2012
Neutrophils are the most abundant leukocytes in circulation and represent one of the first lines of defense against invading pathogens. Neutrophils possess a vast arsenal of antimicrobial proteins, which can be released from the cell by a death program termed NETosis. Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin decorated with granular and cytosolic proteins. Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE), small vessel vasculitis (SVV), and psoriasis. NETs may also represent an important source of modified autoantigens in SLE and SVV. Here, we review the autoimmune diseases linked to NETosis, with a focus on how modified proteins externalized on NETs may trigger loss of immune tolerance and promote organ damage.
Neutrophil extracellular traps (NETs) - formation and implications
Acta Biochimica Polonica, 2013
Neutrophils are cells of the immune system which freely circulate in blood vessels and are recruited to the inflammation sites when the human organism responds to microbial infections. One of the mechanisms of neutrophil action is the formation of neutrophil extracellular traps (NETs) The process of NET generation, called netosis, is a specific type of cell death, different from necrosis and apoptosis. NETs are formed by neutrophils upon contact with various bacteria or fungi as well as with activated platelets or under the influence of numerous inflammatory stimuli, and this process is associated with dramatic changes in the morphology of the cells. The main components of NETs, DNA and granular antimicrobial proteins, determine their antimicrobial properties. The pathogens trapped in NETs are killed by oxidative and non-oxidative mechanisms. On the other hand, it was also discovered that chromatin and proteases released into the circulatory system during NET formation can regulate ...
Molecular and Cellular Biomedical Sciences, 2022
Neutrophil extracellular traps (NETs) are immune components found in a variety of pathological states. It has been shown to have either beneficial or harmful implications, depending on how it is controlled and has been particularly observed in three major scenarios: infection, autoimmune disease, and cancer. In this article, we compiled some of the roles of NETs in pathological conditions, as well as the benefits of targeting them for improved patient outcomes. The role of NETs were primarily positive in infectious disease, whether caused by bacteria, virus, or fungal infection. In non-infectious inflammatory scenarios, on the other hand, it's the complete opposite, with the effects being mainly deleterious and even worse than the original disease states. Targeting NETs directly or indirectly may help to prevent complications and improve patient outcomes. A plethora of compounds, including immunomodulators, anti-thrombosis, nicotinamide adenine dinucleotide phosphate (NADPH)/rea...
A Well-Intentioned Enemy in Autoimmune and Autoinflammatory Diseases: NETosis
Turkish Archives of Pediatrics
Neutrophils are an essential member of the innate immune system derived from the myeloid stem cell series and develop in the bone marrow. The action of neutrophils defined in immune response includes phagocytosis, degranulation, cytokine production, and neutrophil extracellular traps. The success of the host immune defense depends on effective neutrophil activation. Recent studies have shown that neutrophils that have completed their task in the field of inflammation rejoin circulation. Uncontrolled inflammatory response and dysregulated immune responses to the host are important factors in the development of acute and chronic diseases. Neutrophils are the first cells to be drawn into the field at the time of inflammation. They have developed response strategies that produce proinflammatory cytokines and are known as neutrophil extracellular traps since they create mesh-like structures with their DNA contents into the external environment and release their granular proteins in this way. This article summarizes numerous recent studies and reviews the role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases in the hope, that this will lead to the development of more effective treatments. In addition, in this review, the role of neutrophil extracellular trap formation in some pediatric autoimmune diseases is emphasized.