NETosis is a program for formation of neutrophil extracellular traps (NETs), which consist of modified chromatin decorated with bacterial proteins from granules and cytoplasm (1). NETosis is also a form of neutrophil-specific cell death. These NETs that are a part of NETosis, are fairly new, being that they were only discovered in 1996. Neutrophils are considered to be part of the first line of defense of the immune system due to the fact that they are the first cells of the immune system to migrate to a site of inflammation, where they play a key role in pathogen elimination. When they are found in the bloodstream, they have a life span of only 6-8 hours, but when found in tissue they have a lifespan of up to 7 days (4).
There are two fundamentally different forms of NETosis. The first of which is known as classical or suicidal which ultimately leads to cell death. And the secondary is called vital, in which the cells not only remains viably, but it also retains many of its effector functions. NETs formation was initially discovered as a response of neutrophils to the presence of bacteria and instantly their role in prevention of pathogen dissemination was recognized. These NETs consist of chromatin fibers with diameters of 15-17nm that contain DNA and the histones H1, H2A, H2B, H3 and H4 (2). Recent data suggests that NETosis plays a crucial role in the innate immune response and disturbs the homeostasis of the immune system. The induction of NETosis however depends on reactive oxygen species (ROS), the main source of which is NADPH oxidase. Formation of these NETs can be activated by various pathogens, such as bacteria, fungi, protozoa, viruses, as well as bacterial cell wall components-lipopolysaccharides.
Neutrophil granulocytes are the most abundant type of white blood cells in the human body and the play a vital role in innate immunity by defending the host against invading pathogens. Neutrophils are capable of sending the size of the stimuli and can selectively form NETs in response to larger pathogens such as fungi and parasites. When neutrophils undergo NETosis, nuclear and granular membranes disintegrate, the chromatin decondenses, and it diffuses into the cytoplasm, mixing with cytoplasmic proteins. This is then followed by plasma membrane rupture and the release of chromatin, decorated with granular proteins, into the extracellular space. For example, it is now known that in COVID-19, there are an increased formation of neutrophil extracellular traps (NETs), which can be linked to both neutrophil function and dysfunction (3).
Gout is a primary example showing the versatility of NETs. Gout is an autoinflammatory disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. This attracts leukocytes and forms structures known as tophi that mediate tissue damage. The cytokines present in this process not only promote neutrophil recruitment but they also induce NET formation. NET-derived proteases then inactivate cytokines and abrogate their proinflammatory effects after the DNA nets encapsulate MSU crystals and protect them from further phagocytosis (4). In Gout NETs can promote inflammation to aggravate the disease, but they can also regulate the inflammatory process to stop a gout episode as well.
Conclusion is needed here tying this back into OBR and sales, however I am not sure what to say or how to do that.
Sources
- Vorobjeva, N V, and B V Chernyak. “Netosis: Molecular Mechanisms, Role in Physiology and Pathology.” Biochemistry. Biokhimiia, Pleiades Publishing, Oct. 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590568/.
- Yang, Hang, et al. “New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2016.00302/full.
- Pastorek, Michal, et al. “On the Origin of Neutrophil Extracellular Traps in COVID-19.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2022.821007/full.
- Delgado-Rizo, Vidal, et al. “Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview.” Frontiers, Frontiers, 1 Jan. 1AD, https://www.frontiersin.org/articles/10.3389/fimmu.2017.00081/full.