What is NETosis in neutrophil?

What is NETosis in neutrophil?

The formation of neutrophil extracellular traps (NETs) — known as NETosis — can be triggered by microorganisms and endogenous stimuli, such as damage-associated molecular patterns and immune complexes.

What is NETosis and how it develops?

NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bactericidal proteins from granules and cytoplasm. Various pathogens, antibodies and immune complexes, cytokines, microcrystals, and other physiological stimuli can cause NETosis.

What is released during NETosis?

During NETosis, nuclear and granular membranes dissolve, and nuclear contents decondense into the cytoplasm. This is followed by plasma membrane rupture and release of chromatin decorated with granular proteins into the extracellular space(2, 14, 15).

What cells are involved in NETosis?

NETosis was first described in neutrophils, but other cell types including monocytes and macrophages are capable of releasing ETs composed of DNA and antimicrobial proteins. Monocytes/macrophages have been shown to release ETs in a process called METosis [4, 39, 76-78].

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What is Net DNA?

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1,2,3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4,5,6.

How do neutrophils form NETs?

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.

Why is NETosis important?

Vital NETosis allows PMNs to maintain conventional host defensive functions. (A) Conventional neutrophil host response incudes the recruitment cascade, emigration, chemotaxis, phagocytosis, and microbial killing.

Is NETosis real?

Therefore, no real NET formation is observed as a consequence of “NETosis.” Furthermore, such a necrotic-like cell death carries the risk of releasing danger-associated molecular patterns (DAMPs), possibly resulting in excessive inflammation and autoimmunity.

What stimulates NETosis?

Under physiological conditions NETosis can be initiated by a variety of stimuli, including immune complexes, complement activation products, and a milieu of proinflammatory cytokines.

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How do NETs form?

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.

Which cells are associated with NETs?

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.

Who discovered NETosis?

NETosis, which is independent of apoptosis and necrosis, was first observed by Takei et al in 19961. The research team induced NETosis by exposing the neutrophils to PMA1. The bactericidal activity of NETs was uncovered by Brinkmann et al2. Since its discovery, two types of NETosis have been characterized3,11.

What is NETosis and how is it triggered?

Two major NET release mechanisms have been reported, suicidal and vital NETosis. Suicidal NETosis involves the triggering of the Raf-MEK-ERK pathway, NADPH oxidase-dependent pathways, the generation of ROS, and receptor-interacting protein kinase/mixed lineage kinase domain-like-mediated signals [ 18, 19 ].

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Which monoclonal antibodies are used in NETosis?

The most cited monoclonal antibody from each supplier is listed. NETosis is neutrophil-related cell death characterized by the secretion of large web-like structures described as NETs. NETs are composed of chromatin fibers with diameters of 15–17 nm that are made up of DNA and histones H1, H2A, H2B, H3, and H4.

What are netnets in neutrophils?

NETosis is neutrophil-related cell death characterized by the secretion of large web-like structures described as NETs. NETs are composed of chromatin fibers with diameters of 15–17 nm that are made up of DNA and histones H1, H2A, H2B, H3, and H4.

What is the role of ROS in the formation of NETosis?

The exact role of ROS in NETosis formation has not been fully understood, but it is believed to work through two separate mechanisms. Some studies suggest ROS promote the morphological changes noted during NETosis [ 15 ].