Network of extracellular traps in the pathogenesis of sterile chronic inflammatory diseases: Role of oxidative stress and potential clinical applications.

Abstract

ETs are scaffold of DNA decorated with histones and granular proteins extruded by immune cells in response to various stimuli. One of the mechanisms by which these immune cells have an adverse effect on outcomes of chronic inflammation is through the generation of extracellular traps (ETs), which facilitate release of nuclear chromatin, reactive oxygen species (ROS), and bioactive proteins into the extracellular matrix. The phenomenon of ETs formation has been reported in various immune cells and excessive reactive oxygen species (ROS) produced during the activation of these cells can induce extensive DNA damage leading to chromosome decondensation. Inflammatory milieu can promote the production of ROS and ETs reshaping the tissue microenvironment. Recent studies have shown that ETs can facilitate persistent inflammation, angiogenesis and promote thrombosis. The present review describes role of ETs in pathogenesis of chronic inflammatory diseases. It summarizes the ROS-dependent and independent mechanisms and context of ET formation, role of ETs produced by different immune cells in the inflammatory tissue environment and response to various therapies. The importance of putative ETs as predictive or prognostic biomarkers and upcoming prophylactic strategies targeting ETs in patients with chronic inflammation is discussed. Future research to elucidate the mechanisms that cause ETs to resolve inflammation in normal physiology and mechanisms that cause aberrant ETs formation in persistent inflammation is needed. Large-scale clinical studies about role of ETs in diagnosis and prognosis of inflammatory diseases can be performed to understand their potential role as biomarkers.