NETs: Immune Defences Turned Inside-Out Event

Speaker: Dr Stephen Clark, Lecturer in Immunopharmacology, Cardiff School of Pharmacy & Pharmaceutical Sciences

Abstract : Neutrophil extracellular traps (NETs) are web-like structures of DNA and protein that play a critical role in catching and killing pathogens including bacteria, fungi and viruses. While there is much interest in the process of NET-formation at foci of infection, less well understood is the significance of NET formation within blood vessels during systemic inflammation and sepsis.

When bacteria escape the initial immune response and make it into the circulation, they are cleared by NETs in the microvasculature of the lungs and liver. The platelet is an essential regulator of intravascular NET formation. Adding further complexity to the role of NETs in sepsis, NETs provide a scaffold and stimulus for thrombus formation; this may aid in containment of infection but could also contribute to disseminated intravascular coagulation in sepsis.

Due to the association of NETs with organ damage and autoimmune diseases, there may be benefit in breaking down or inhibiting these structures if other microbial defences or antibiotics can control the infection. One approach is to develop therapeutics that prevent NETs from being released. Hydroxyhwsosatetraenoic-phosphatidylethanolamine (HETE-PE) is a recently identified endogenous inhibitor of NETs that is produced in the membranes of neutrophils by 5-lipoxygenase.

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