Neutrophil extracellular traps as the main source of eDNA

Abstract

Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed DNA together with accompanying proteins, including histones and antimicrobial peptides released from activated neutrophils as part of the first-line defence against pathogens. Despite the protective role of neutrophils, a number of studies indicate that overproduction of NETs followed by accumulation of extracellular DNA (eDNA) and other negatively-charged polyelectrolytes (PE) such as F-actin, contribute to the pathogenesis of some diseases. Neutrophil extracellular traps are also recognised as the structural and functional support of microbial biofilms and should thus be considered as therapeutic targets. Importantly, the chemical nature of PE permits aggregate formation induced by a number of polycations occurring naturally in the human body, including cationic antimicrobial peptides. This review summarises recent reports focused on the clinical significance of NET-derived eDNA and PE and discusses the potential therapeutic strategies to limit the negative consequences of eDNA accumulation.

Extracellular DNA in natural environments: features, relevance and applications

“…On the other hand, exDNA has been shown to act as a trap for invading pathogens in the shape of NETs, being in that way a part of the innate immune system and combatting an infection. The same benign NETs can cause, however, pathophysiological effects in cancer, autoimmune pathologies, sepsis, thrombotic illness and in the inflammatory response through different mechanisms, as highlighted above (Ciesluk et al 2017 ; Cooper et al 2013 ; Park et al 2016 ).…”

“…In addition, exDNA was found to act as a trap for infectious organisms in mammalians (reviewed by Ciesluk et al 2017) and during root tip growth of plants (Hawes et al 2012; Pietramellara et al 2013). Finally, exDNA is assumed to act as a species-specific growth inhibitor all over the tree of life (Mazzoleni et al 2015b; esDNA).…”

“…Extracellular DNA has also been investigated within dead wood (Gómez-Brandón et al 2017a ), cattle rumen and manure (Chroňáková et al 2013 ; Fliegerová et al 2014 ; Nagler et al 2018 ), aerobic and anammox granules (Cheng et al 2011 ; Xiong and Liu 2012 ; Dominiak et al 2011 ) and human epithelial cells used in forensics (Wang et al 2017 ). In addition, exDNA was found to act as a trap for infectious organisms in mammalians (reviewed by Ciesluk et al 2017 ) and during root tip growth of plants (Hawes et al 2012 ; Pietramellara et al 2013 ). Finally, exDNA is assumed to act as a species-specific growth inhibitor all over the tree of life (Mazzoleni et al 2015b ; esDNA).…”

Decreased Activity of Blood Acid Sphingomyelinase in the Course of Multiple Myeloma

“…The major part of apoptosis among sphingolipids is ceramide. It affects the aggregation of the death receptor in the plasma membrane and the formation of pores in the mitochondria [23,24].…”

Bactericidal and immunomodulatory properties of magnetic nanoparticles functionalized by 1,4-dihydropyridines

“…As presented here, antimicrobial activity of 1,4-DHP derivatives was determined by the high affinity of these compounds to the bacterial membrane and potential possibility to penetrate biopolymer network. 46,47 Moreover, the synergistic effects of nanoparticles and antibiotics have been extensively reported in the literature. 48 Our previous report showed that the combination of antibacterial agents with MNPs increases their bactericidal effect.…”