NETosis and ETosis

Incompletely understood types of granulocyte death and their proposed adaptive benefits and costs

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Neutrophilic granulocytes (neutrophils) are an important cell type of the innate immune system. They are the most numerous white blood cells, and their exit from the vasculature (extravasation) at a site of a localized infection serves to combat microbial pathogens. The extravasated neutrophils serve to set up a localized area of elevated temperature, redness, swelling and pain, a set of manifestations that define inflammation. Endogenous stimuli for neutrophil extravasation also exist and can contribute to chronic inflammatory diseases. In tissues, neutrophils migrate along a gradient of chemotactic signals until they reach the source of the stimulus, usually the infectious organism itself. Upon contact, the neutrophils respond by executing a complex series of cellular mechanisms that capture and destroy the pathogen. One proposed mechanism requires the neutrophils to perform an elaborate type of suicide. In this regulated process, neutrophils decondense nuclear chromatin and rupture cellular membranes, leading to the release of chromatin from the cell. The released chromatin forms an extracellular matrix that has the capacity to immobilize ‐ or “trap” ‐ the microbial pathogens. The neutrophil extracellular traps, abbreviated as NETs, give this type of cell death its name. NETosis was first observed in neutrophils but other cells of the innate immune system, such as eosinophils, basophils and macrophages, may share this mechanism of cell death. Therefore, NETosis sometimes loses one of its initials and is more broadly referred to as ETosis. Notably, ETosis is conserved through evolution, as vertebrates, invertebrates and even plants use nuclear chromatin as defense against microbial intruders. This chapter gives a history of NETosis, the current understanding of its regulation, and its functions in infections. A comparison to other types of cell death, such as necroptosis and apoptosis, is provided. In addition, the chapter summarizes the consequences of inappropriate or excessive NETosis which may lead to chronic inflammation and autoimmune disease. A survey of approaches to develop pharmacological inhibitors of NETosis is given and open questions are discussed at the conclusion of this chapter.

Original languageEnglish (US)
Title of host publicationApoptosis and Beyond
Subtitle of host publicationThe Many Ways Cells Die
Publisherwiley
Pages511-534
Number of pages24
ISBN (Electronic)9781119432463
ISBN (Print)9781119432425
DOIs
StatePublished - Jan 1 2018

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Granulocytes
Chromatin
Cost-Benefit Analysis
Pathogens
Cell death
Immune system
Costs
Cell Death
Macrophages
Immune System
Chronic Disease
Swelling
Blood
Inflammation
Cells
Tissue
Apoptosis
Membranes
Basophils
Invertebrates

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

NETosis and ETosis : Incompletely understood types of granulocyte death and their proposed adaptive benefits and costs. / Radic, Marko.

Apoptosis and Beyond: The Many Ways Cells Die. wiley, 2018. p. 511-534.

Research output: Chapter in Book/Report/Conference proceedingChapter

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