Neutrophil extracellular traps (NETS): role in disease

Neutrophil extracellular traps (NETs) are web-like structures composed by a chromatin backbone, histones and antimicrobial proteins. NETs constitute yet another mechanism deployed by neutrophils to immobilise and kill microorganisms, thus contributing to the host innate immunity. Neutrophils cast NETs upon stimulation by a variety of stimuli, including bacteria, protozoa, fungi, viruses, their products and also host factors like chemokines, complement and activated platelets. NETs production or NETosis occurs as a result of activation of neutrophil PKC, Raf-MEK-ERK and NADPH oxydase signalling pathways. Driven mostly by peptidylarginine deiminase 4 (PAD4) citrullination of histones, the hallmark of NETosis is chromatin decondensation, rupture of nuclear membrane and release of nuclear and granular contents into the cytoplasm, prior their release into the extracellular space. NETs control propagation of pathogens by entrapping them within the lose chromatin web and kills them with the antimicrobial molecules –granule proteins and histones- present in high concentrations within the chromatin network. Despite contributing to host defence, aberrant NET formation may damage tissues and activate inflammatory cells, contributing to several pathologies, including sepsis, systemic inflammatory response syndrome, autoimmune diseases and thrombosis. This review presents an overview of our current knowledge of NETs physiology and their role in fighting and propagating disease.Sociedad Argentina de FisiologíaFacultad de Ciencias Médica