Target intelligence / Profile preview

Neutrophil extracellular trap DNA (NET-DNA) (NET-DNA)

Target
NET-DNA
Molecular classification
Nucleic acid, Extracellular matrix component, Biopolymer
01

Overview

Neutrophil extracellular trap DNA (NET-DNA) is the double-stranded DNA scaffold that forms the structural backbone of web-like fibers released by activated neutrophils during a specialized cell death process known as NETosis (Brinkmann et al., 2004). These traps are decorated with antimicrobial proteins, such as neutrophil elastase and myeloperoxidase, and histones, serving a vital role in the innate immune system by capturing and neutralizing various pathogens (Papayannopoulos, 2018). However, the excessive or persistent presence of NET-DNA is a significant driver of pathology in conditions like cystic fibrosis, where it increases mucus viscosity, and systemic lupus erythematosus, where it serves as a source of autoantigens (Knight et al., 2012). In cardiovascular diseases, NET-DNA acts as a pro-thrombotic lattice that promotes the formation of immunothrombi (Fuchs et al., 2010). Therapeutic strategies targeting NET-DNA primarily involve the use of deoxyribonuclease (DNase) enzymes, such as dornase alfa, which enzymatically degrade the DNA backbone to dissolve the traps and reduce inflammation and tissue damage (Zuo et al., 2020).

Other names
Extracellular double-stranded DNA in Neutrophil Extracellular TrapsNET-associated DNAExtracellular DNA (eDNA)Neutrophil extracellular trapsNETs
02

Mechanism of action

Enzymatic hydrolysis of the phosphodiester backbone of extracellular double-stranded DNA, leading to the dissolution of the neutrophil extracellular trap scaffold.

03

Biological functions

Immune responsePathogen entrapmentAntimicrobial activityPro-inflammatory signaling
04

Disease associations

Cystic fibrosisSystemic lupus erythematosusThrombosisCancer metastasisCOVID-19SepsisRheumatoid arthritisAsthma
05

Safety considerations

Increased risk of systemic infection or bacteremia due to loss of pathogen containmentPotential release of sequestered cytotoxic granule proteins (e.g., elastase) into systemic circulationImpairment of normal innate immune defense mechanisms
06

Interacting drugs

Dornase alfa

3 more in the full profile.

07

Biomarkers

Citrullinated histone H3 (H3Cit)Myeloperoxidase-DNA (MPO-DNA) complexesNeutrophil elastase-DNA (NE-DNA) complexesCell-free DNA (cfDNA)

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