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L-64 - Reactive oxygen species ameliorate the clinical course of murine lupus.
- Source :
-
Free Radical Biology & Medicine . May2018 Supplement 1, Vol. 120, pS22-S22. 1p. - Publication Year :
- 2018
-
Abstract
- Systemic lupus erythematosus (SLE) is characterized by autoimmune reactivity against components of the cell's nucleus arising after insufficient removal of dead cells. We used a lupus mouse model induced by the cytotoxic alkane oil pristane to elucidate the impact of ROS on SLE. Pristane-induced lupus was strongly exacerbated in NOX2-deficient (Ncf1**) compared to wild type mice, as seen from elevated levels of antinuclear autoantibodies (ANA), aggravated organ damage, and premature death. We observed a dramatically reduced ability to form neutrophil extracellular traps (NETs) in Ncf1** mice, accompanied by higher levels of inflammatory mediators. Similarly, NET-deficient peptidyl arginine deiminase 4-deficient mice and neutropenic Mcl-1 ΔMyelo mice exhibited higher levels of ANA, which indicates a regulatory function in lupus of NETs and neutrophils, respectively. Furthermore, Ncf1** mice and SLE patients displayed preferential uptake of dead cells into inflammatory monocytes and granulocytes. Treatment of mice with NOX2 activators induced NET formation and ameliorated lupus. Our results show that absence of ROS leads to lupus based on aberrant phagocytosis of dead cell remnants and impaired formation of NETs, which results in uncontrolled release of inflammatory mediators. [ABSTRACT FROM AUTHOR]
- Subjects :
- *REACTIVE oxygen species
*SYSTEMIC lupus erythematosus
*CYTOKINES
Subjects
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 120
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 131112709
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2018.04.093