Neutrophil extracellular trap pathway (NET pathway)

The Neutrophil extracellular trap (NET) pathway is a specialized innate immune process where neutrophils release extracellular fibers composed of decondensed chromatin decorated with antimicrobial proteins, such as neutrophil elastase and myeloperoxidase, to ensnare and eliminate pathogens [1, 2]. This process, often termed NETosis, is triggered by various stimuli including microbes, cytokines, and immune complexes, involving key enzymes like Peptidylarginine deiminase 4 (PAD4) which facilitates chromatin decondensation [3]. While NETs are vital for host defense, their dysregulation or persistence is linked to the pathogenesis of autoimmune diseases like systemic lupus erythematosus, where they promote the loss of self-tolerance, and to thrombotic disorders where they act as scaffolds for clot formation [4]. In oncology, NETs have been shown to shield tumor cells from cytotoxicity and promote metastasis [5]. Therapeutic targeting of this pathway involves either the enzymatic degradation of existing NETs using DNases or the inhibition of intracellular enzymes required for their formation, aiming to mitigate tissue damage and chronic inflammation [2, 4].

Other names

NETosisNeutrophil extracellular trapsNET formationExtracellular trap formation

Degradation of extracellular DNA scaffolds or inhibition of enzymes (e.g., PAD4, Neutrophil elastase) essential for chromatin decondensation and trap release.