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