Research Article: An opsonic peptide promotes radiation-induced macrophage extracellular trap clearance to alleviate inflammation
Abstract:
Ionizing radiation exposure leads to inflammation and tissue damage, in which macrophage extracellular traps (METs) may play a role. Effective strategies to mitigate inflammation caused by radiation-induced METs are needed. We have recently developed a novel opsonic peptide, OP18, that targets multiple damage-associated molecular patterns (DAMPs) and enhances their clearance by macrophages. Because METs contain DAMPs, including histone H3 and high-mobility group box 1 protein (HMGB1), we hypothesize that OP18 promotes the clearance of radiation-induced METs and thereby reduces inflammation. In vitro studies were conducted using macrophages exposed to radiation and METs, with or without OP18 treatment. METs uptake, endo-lysosomal trafficking, integrin involvement, mitochondrial function, NF-?B activation, and cytokine release were assessed. OP18 significantly enhances MET uptake by macrophages, an effect that is mediated by ? v ? 3 -integrin and involves the endo-lysosomal trafficking. This enhanced clearance by OP18 alleviates METs-induced mitochondrial stress and restores metabolic function (ATP production, basal/maximal respiration) in macrophages. Furthermore, OP18 treatment exhibits a trend towards decreasing METs-induced NF-?B activation while increasing the release of anti-inflammatory cytokine IL-10. OP18 represents a novel therapeutic approach to mitigate radiation-induced inflammation by promoting the efficient clearance of pro-inflammatory METs, thereby restoring cellular homeostasis and dampening inflammatory signaling.
Introduction:
Life-threatening ionizing radiation can result from catastrophic events such as nuclear detonations, severe reactor or criticality accidents, unshielded industrial radiation sources, radiotherapy misadministration, and extreme solar particle events in space ( 1 ). Within living tissues, ionizing radiation exerts its detrimental effects by disrupting chemical bonds within molecules. This molecular disruption primarily damages cellular processes and, critically, DNA structure, forming the basis of its profound…
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