Extracellular DNA within neutrophil extracellular traps (NET-DNA) (NET-DNA)

Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed chromatin (DNA and histones) and antimicrobial proteins released by neutrophils to capture and kill pathogens [1.1.1, 1.4.1]. While essential for innate immunity, excessive or persistent NET-DNA acts as a pro-inflammatory and pro-thrombotic scaffold, contributing to the pathogenesis of various diseases including sepsis, systemic lupus erythematosus (SLE), and thrombosis [1.1.1, 1.2.2]. In conditions like cystic fibrosis, the accumulation of NET-DNA in the airways increases mucus viscosity and impairs lung function [1.2.2, 1.4.2]. Therapeutic strategies primarily involve the use of deoxyribonucleases (DNases), such as dornase alfa, which enzymatically degrade the DNA backbone to dissolve the traps and reduce their pathological effects [1.2.4, 1.4.2]. Emerging research also explores the role of NET-DNA in cancer metastasis and its potential as a biomarker for disease severity in acute conditions like COVID-19 [1.3.4, 1.4.1]. The presence of NET-DNA in the circulation or tissues can be monitored using biomarkers such as myeloperoxidase-DNA complexes or citrullinated histone H3 [1.3.2, 1.4.2].

Other names

Neutrophil extracellular trapsNETsCell-free DNA (cfDNA)NET-associated DNAExtracellular chromatin

Enzymatic degradation of the DNA phosphodiester backbone by deoxyribonucleases (DNases), which dissolves the structural scaffold of the neutrophil extracellular trap and facilitates the clearance of associated proteins and trapped pathogens [1.2.4, 1.4.2].