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Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Aggravation of experimental allergic encephalomyelitis (EAE) by administration of nitric oxide (NO) synthase
S R Ruuls1, S Van Der Linden, K Sontrop
1Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
Macrophages constitute a large proportion of the inflammatory cells that infiltrate the central nervous system (CNS) of animals with EAE. Through the production of inflammatory mediators these infiltrating macrophages can contribute to the regulation of the immune reaction within the CNS, that eventually results in neurological deficits associated with EAE. NO, a free radical produced by macrophages and other cell types, has been put forward as such an immune mediator. In the present study we show that macrophages isolated from the CNS of Lewis rats with clinical signs of EAE produce elevated amounts of NO. We treated rats, in which EAE was induced, with N(omega) -nitro-L-arginine-methylester or N(g)-monomethyl-L-arginine, inhibitors of NO synthase, either systemically via intraperitoneal injection, or intracerebrally via a cannula placed in the lateral ventricle. Both treatments resulted in a marked aggravation of clinical signs of EAE. These data point to an important role of NO, produced by infiltrating macrophages, as an immune-suppressor in the disease process during EAE.
Insights
Nitric oxide (NO), produced by macrophages in the central nervous system (CNS), acts as an immune-suppressor in experimental autoimmune encephalomyelitis (EAE). Inhibiting NO production worsened EAE clinical signs in rats, highlighting NO's protective role.
Area of Science:
- Neuroimmunology
- Inflammation Research
- Central Nervous System (CNS) Disorders
Background:
- Macrophages infiltrate the CNS during EAE, releasing mediators that influence the immune response.
- Nitric oxide (NO) is a free radical produced by macrophages and implicated as an immune mediator in CNS diseases.
- Neurological deficits in EAE are linked to the inflammatory response within the CNS.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) produced by macrophages in the pathogenesis of experimental autoimmune encephalomyelitis (EAE).
- To determine if NO acts as an immune-suppressor or immune-enhancer in the context of EAE.
Main Methods:
- Isolated macrophages from the CNS of Lewis rats exhibiting clinical signs of EAE.
- Quantified NO production by these macrophages.
- Administered NO synthase inhibitors (Nω-nitro-L-arginine-methylester or Nγ-monomethyl-L-arginine) systemically or intracerebrally in rats with induced EAE.
Main Results:
- Macrophages from EAE rats' CNS showed elevated NO production.
- Inhibition of NO synthase led to a significant aggravation of clinical signs in EAE rats, regardless of administration route (systemic or intracerebral).
Conclusions:
- NO produced by infiltrating macrophages plays a crucial immunosuppressive role in the EAE disease process.
- Targeting NO production could potentially exacerbate EAE, suggesting NO is protective.
- These findings underscore the complex immunomodulatory functions of macrophages in CNS autoimmunity.
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