YO-10 - ROS is the boss

Abstract

The production of reactive oxygen species (ROS) via the oxidative burst has been connected with promotion of inflammation and tissue damage, but in recent years has been implicated in regulation of inflammation. We investigated the effects of ROS on the murine model of lupus and in patients (SLE). The aim of this project was to elucidate the impact of the oxidative burst on the development of lupus-like autoimmunity. Lupus was induced by i.p. injection of pristane oil. Ex vivo phagocytosis assays were deployed to assess the uptake of cell debris in ROS deficient mice. The formation of neutrophil extracellular traps (NETs) was analysed by immune fluorescence microscopy. ROS activators were injected into mice to investigate the possible beneficial clinical effects on lupus pathology. The absence of ROS gives rise to dramatically exacerbated lupus. Aberrant phagocytosis in ROS-deficient animals leading to production of inflammatory mediators, accompanied by diminished pristane-induced but higher spontaneous formation of NETs could be responsible for this phenotype. Treatment with NOX2 agonists ameliorated the clinical course in mice, while application of a ROS scavenger worsened disease outcome. A fine-tuned balance of ROS-production is necessary to prevent autoimmunity and to avert the development of lupus in mice and men.