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The Impact of Age on Neutrophil Extracellular Trap Formation

  • Jon Hazeldine
  • Janet M Lord
Living reference work entry

Abstract

Neutrophils are the most abundant leukocyte in blood and play a key role in the defense against rapidly dividing bacteria, yeast, and fungi. It was thought previously that neutrophils provided this frontline protection only via three intracellular microbicidal mechanisms: phagocytosis, degranulation, and the generation of reactive oxygen species (ROS). However, in 2004, Brinkmann and colleagues revealed an extracellular antimicrobial mechanism of neutrophils, termed neutrophil extracellular traps. When challenged with an array of inflammatory agonists such as proinflammatory cytokines (IL-8/CXCL8), bacterial cell wall protein lipopolysaccharide (LPS), Gram-negative bacteria, or PMA, neutrophils expel into the extracellular environment their nuclear DNA decorated with a multitude of granule-derived proteases (e.g., neutrophil elastase (NE)) and peptides (e.g., lactoferrin). As such, NETs are able to capture Gram-positive and -negative bacteria and disarm their virulence factors. NET formation is thought to be a last resort of the neutrophil and is not without its negative consequences as this process of netosis exposes the immune system to a range of self-antigens normally hidden within the cell. Netosis has thus been linked with breakdown of tolerance in autoimmune conditions such as rheumatoid arthritis. NET formation is reduced in older adults and also during the immune paresis seen after major trauma. In both situations, this may be linked to increased infection susceptibility. Pharmaceutical approaches to enhance netosis need to be considered with caution, as if the mechanisms to clear the resulting cell free DNA are not enhanced in parallel there is risk of thrombosis and damage to vital organs.

Keywords

Neutrophil NETs Ageing Trauma Infection Netosis 

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.NIHR Surgical Reconstruction and Microbiology Research Centre and Institute of Inflammation and AgeingUniversity of BirminghamBirminghamUK

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