The role of nitric oxide in abnormal T cell signal transduction in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of antinuclear autoantibodies and diverse array of clinical manifestations. T cells from patients with SLE have been shown to be activated in vivo and provide help to autoreactive B cells. Lupus T cells exhibit enhanced spontaneous and diminished activation-induced apoptosis and predisposition to necrosis. Persistent mitochondrial hyperpolarization and ATP depletion - associated with significantly increased mitochondrial mass - characterize T lymphocyte dysfunction in SLE. In addition to cell death abnormalities, mitochondrial dysfunction is associated with altered signal transduction through the T cell receptor and Ca2+ fluxing. Exposure of normal T cell to nitric oxide induces mitochondrial hyperpolarization and biogenesis and regenerates the Ca2+ signaling profile of lupus T cells. This article reviews a novel understanding of the role of nitric oxide in signal transduction and cell death abnormalities in SLE.
Nagy
Gyorgy
G
Section of Rheumatology, Department of Medicine, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.
Perl
Andras
A
D000818:Animals; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*
D009569:Nitric Oxide