NET formation – mechanisms and how they relate to other cell death pathways

Rosazza, Thibault; Warner, Jordan; Sollberger, Gabriel

doi:10.1111/febs.15589

Cited by 53 publications

(52 citation statements)

References 135 publications

(173 reference statements)

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“…The situation is further complicated by the fact that NET formation can take place even in the absence of necrosis. In other words, the development of NETs in humans occurs independently without the signaling of RIPK3 and MLKL, and the process is therefore independent of necroptosis 11 , 12 . Nevertheless, NETosis is considered a critical process that helps eliminate disease-causing pathogens.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Vasculitis

Arneth

2021

Int. J. Med. Sci.

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Background: Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. Aim: This study aimed to explore the relationship between NETs and vasculitis. Material and Methods: The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included “vasculitis,” “NETs,” “neutrophil extracellular traps,” “NETosis,” and “pathogenesis.” The search was limited to articles published between 2009 and 2019. Results: Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Discussion: Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Conclusion: Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.

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Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) and Vasculitis

Arneth

2021

Int. J. Med. Sci.

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“…Although ETs are widely studied, NETs are a complex phenomenon, and there are still questions to be elucidated about the mechanisms involved in their formation (origin of the DNA, programmed cell death, signaling pathways), their role in host defense, and the pathophysiology of some diseases [6]. Many studies have been carried out in recent years; however, factors, such as the origin of the neutrophils used in the experiments, the isolation methods, the culture media, and/or the cell reactivation may influence the results, making it difficult to compare the results and the outline of unified knowledge about NETs [54,55]. Despite variations in nomenclature and classification, the mechanisms can share pathways, resulting in the release of extracellular DNA [2,5,10,20,22,23,55].…”

Section: Neutrophilsmentioning

confidence: 99%

Section: Neutrophilsmentioning

confidence: 99%

“…NETs can also be classified as NADPH (NOX)-dependent and NOX-independent according to ROS production, since the presence or absence of ROS produced by NADPH oxidase in the cytoplasm or mitochondria seems to influence their formation [3][4][5]22,23,54]. In the formation of NOX-dependent NETs, various stimuli (e.g., PMA, cholesterol crystals, fungi, bacteria) induce ROS production by NADPH oxidase [10,23,54,55]. It has been found that NOX-independent NETs formation can be induced by calcium ionophores (e.g., A23128, A23187, ionomycin), uric acid crystals, nicotine, and immune complexes [22,25,55,60], but it is still questionable whether these mechanisms are ROS-independent, or whether mitochondrial ROS (mtROS) are produced [54].…”

Section: Neutrophilsmentioning

confidence: 99%

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The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection

Conceição-Silva

Reis

Luca

et al. 2021

Cells

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The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described—suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.

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“…However, the coexistence of dead vs viable, two types of NET formation, remains controversial. Thus, a recent consensus review article published by tens of investigators in NET formation research field suggested using the term "NET formation" instead of NETosis to cover the phenomenon of DNA release from neutrophils with or without cell death (26,27). Here, we will mainly focus on the dead NETotic neutrophils that release their nuclear chromatin to form extracellular NETs.…”

Section: Introduction -Netosis and Extracellular Net Formationmentioning

confidence: 99%

Recent progress in the mechanistic understanding of NET formation in neutrophils

2021

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Neutrophils are the most abundant circulating white blood cells and one of the major cell types of the innate immune system. Neutrophil extracellular traps (NETs) are a result of the extracellular release of nuclear chromatin from the ruptured nuclear envelope and plasma membrane. The externalized chromatin is an ancient defense weapon for animals to entrap and kill microorganisms in the extracellular milieu, thus protecting animals ranging from lower invertebrates to higher vertebrates. Although the externalized chromatin has the advantage of acting as anti-infective to protect against infections, extracellular chromatin might be problematic in higher vertebrate animals as they have an adaptive immune system that can trigger further immune or autoimmune responses. NETs and their associated nuclear and/or cytoplasmic components may induce sterile inflammation, immune and autoimmune responses, leading to various human diseases. Though important in human pathophysiology, the cellular and molecular mechanisms of NET formation (also called NETosis) are not well understood. Given that nuclear chromatin forms the backbone of NETs, the nucleus is the root of the nuclear DNA extracellular traps. Thus, nuclear chromatin decondensation, along with the rupture of nuclear envelope and plasma membrane are required for nuclear chromatin extracellular release and NET formation. So far, most of the literature focuses on certain signaling pathways which are involved in NET formation but without explanation of cellular events and morphological changes described above. Here, we have summarized emerging evidence and discuss new mechanistic understanding, with our perspectives, in NET formation in neutrophils.

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NET formation – mechanisms and how they relate to other cell death pathways

Cited by 53 publications

References 135 publications

Neutrophil Extracellular Traps (NETs) and Vasculitis

Neutrophil Extracellular Traps (NETs) and Vasculitis

The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection

Recent progress in the mechanistic understanding of NET formation in neutrophils

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