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Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats
S R Ruuls1, J Bauer, K Sontrop
1Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, Netherlands.
Abstract:
During experimental allergic encephalomyelitis (EAE), both blood-borne macrophages as well as activated, resident microglial cells are considered to be involved in inflammatory reactions in the central nervous system (CNS), resulting in the neurological deficits common to EAE. Both cell types can produce multiple mediators of tissue damage, among which are the reactive oxygen species (ROS). In this study we show that macrophages and microglial cells, isolated from the CNS of Lewis rats with clinical signs of EAE, exhibited significantly elevated spontaneous and phorbol myristate acetate (PMA)-inducible levels of ROS compared to similar cells isolated from healthy controls, sham (complete Freund's adjuvant, CFA)-immunized rats as well as rats sacrificed before the manifestation of clinical signs of EAE. However, during clinical EAE, peripheral blood mononuclear cells (PBMC) did not show increased spontaneous nor PMA-inducible ROS production compared to controls. In vivo treatment of EAE with catalase, which scavenges the ROS H2O2, markedly suppressed the severity of the disease as compared to sham (albumin)-treated controls. In contrast, superoxide dismutase had no effect on clinical signs. Our studies point at a putative functional role for ROS, and in particular H2O2, in the pathogenesis of EAE.
Insights
Reactive oxygen species (ROS) are elevated in the central nervous system during experimental allergic encephalomyelitis (EAE). Catalase treatment reduced disease severity, suggesting a role for hydrogen peroxide (H2O2) in EAE pathogenesis.
Area of Science:
- Neuroimmunology
- Oxidative Stress
- Central Nervous System Inflammation
Background:
- Experimental allergic encephalomyelitis (EAE) involves macrophages and microglia in CNS inflammation and neurological deficits.
- Reactive oxygen species (ROS) are implicated as mediators of tissue damage in inflammatory conditions.
Purpose of the Study:
- To investigate the role of ROS, specifically hydrogen peroxide (H2O2), in the pathogenesis of EAE.
- To determine if ROS production by CNS-resident and blood-borne immune cells is altered during EAE.
Main Methods:
- Isolated macrophages and microglial cells from Lewis rats with EAE and controls.
- Measured spontaneous and phorbol myristate acetate (PMA)-inducible ROS production.
- Administered catalase and superoxide dismutase in vivo to EAE rats.
Main Results:
- CNS macrophages and microglia from EAE rats showed significantly elevated ROS levels compared to controls.
- Peripheral blood mononuclear cells (PBMC) did not exhibit increased ROS production during EAE.
- In vivo catalase treatment markedly suppressed EAE severity, while superoxide dismutase had no effect.
Conclusions:
- Elevated ROS, particularly H2O2, in CNS-resident immune cells may play a functional role in EAE pathogenesis.
- Targeting H2O2 with catalase shows therapeutic potential for EAE.