Network of Extracellular Traps in the Pathogenesis of Sterile Chronic Inflammatory Diseases: Role of Oxidative Stress and Potential Clinical Applications

Antioxid Redox Signal. 2023 Nov 7. doi: 10.1089/ars.2023.0329. Online ahead of print.

Abstract

Significance: Extracellular traps (ETs) represent structured frameworks that comprised DNA embellished with histones and granular proteins extruded by immune cells in response to various stimuli. Immune cells contribute to adverse effects of chronic inflammation via ET generation, promoting the release of nuclear chromatin, reactive oxygen species (ROS), and bioactive proteins into the extracellular matrix. Recent Advances: The occurrence of ET formation has been documented across diverse immune cell types. The excessive production of ROS during the activation of these cells has the potential to initiate substantial DNA damage, culminating in chromosome decondensation. The inflammatory microenvironment fosters ROS and ET generation, impacting tissue microenvironment remodeling. Recent studies reveal ET involvement in sustaining persistent inflammation, promoting angiogenesis, and initiating thrombotic processes. Critical Issues: This review elucidates ET participation in chronic inflammatory disease etiology, detailing ROS-dependent and ROS-independent ET formation mechanisms and their contextual manifestations. It discusses diverse immune cell-derived ETs in the inflammatory milieu and their responses to therapies. Furthermore, the review emphasizes the significance of ETs as potential biomarkers and envisions prophylactic strategies against ET-associated chronic inflammation. Future Directions: Subsequent investigations are warranted to uncover the intricate mechanisms governing the resolution of inflammation through ETs in normal physiological processes. Moreover, a comprehensive understanding of the aberrant pathways driving ET formation in persistent inflammation is imperative. Prospective research endeavors should focus on executing expansive clinical studies to discern the involvement of ETs in both the diagnostic and prognostic facets of inflammatory diseases, thereby shedding light on their prospective utility as biomarkers.

Keywords: ETosis; chronic inflammation; extracellular traps (ET); immune cells; reactive oxygen species (ROS).