Extracellular DNA and Neutrophil Extracellular Traps (eDNA/NETs)

Extracellular DNA (eDNA) and Neutrophil Extracellular Traps (NETs) are major structural components of the thick, viscous mucus found in the airways of patients with chronic inflammatory lung diseases such as cystic fibrosis and severe asthma. NETs are web-like networks composed of decondensed chromatin (DNA and histones) decorated with antimicrobial proteins like neutrophil elastase and myeloperoxidase, which are released by neutrophils to capture and kill pathogens. However, their excessive accumulation in the respiratory tract significantly increases the viscoelasticity of mucus, leading to airway obstruction, impaired mucociliary clearance, and a cycle of persistent infection and inflammation. Therapeutic strategies target this eDNA primarily through the use of recombinant human DNase I (Dornase alfa), which enzymatically cleaves the DNA backbone to liquefy the mucus and facilitate its expectoration. Beyond cystic fibrosis, targeting eDNA and NETs is being investigated as a treatment for other conditions characterized by neutrophilic inflammation, including COPD, ARDS, and COVID-19-related respiratory failure.

Other names

Extracellular DNANeutrophil extracellular trapseDNANETsExtracellular chromatinNeutrophil trapsCell-free DNA in sputum

Enzymatic hydrolysis of extracellular DNA phosphodiester bonds to reduce mucus viscosity and improve airway clearance.