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Macrophage apoptosis in the central nervous system in experimental autoimmune encephalomyelitis
K B Nguyen1, P A McCombe, M P Pender
1Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.
Abstract:
Using light and electron microscopy, we have demonstrated that macrophage apoptosis (programmed cell death) occurs in the central nervous system (CNS) in Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) and chronic relapsing EAE. Apoptotic macrophages were identified by the presence of an apoptotic nucleus in a cell with cytoplasm containing myelin debris but no intermediate filaments. They were found in the meninges, perivascular spaces and in the parenchyma of the white and grey matter of the spinal cord. In acute EAE the apoptotic macrophages were most frequently seen at the time of maximal neurological signs and during the early stages of clinical recovery. Several possible mechanisms may be responsible for the macrophage apoptosis: the release or withdrawal of cytokines; T-cell cytotoxicity; the effect of activated macrophage products, such as nitric oxide; and a direct effect of endogenous glucocorticoids. Macrophage apoptosis, together with the T-cell apoptosis we have previously described in the CNS in EAE, may contribute to the down-regulation of this autoimmune disease.
Insights
Macrophage apoptosis, or programmed cell death, occurs in the central nervous system during experimental autoimmune encephalomyelitis (EAE). This process may help regulate this autoimmune disease.
Area of Science:
- Neuroimmunology
- Cell Biology
- Pathology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis.
- Macrophage infiltration and activation are key features of EAE pathogenesis.
- The fate of macrophages within the central nervous system (CNS) during EAE is not fully understood.
Purpose of the Study:
- To investigate the occurrence and localization of macrophage apoptosis in the CNS during EAE.
- To identify potential mechanisms driving macrophage apoptosis in EAE.
- To understand the role of macrophage apoptosis in the resolution of EAE.
Main Methods:
- Light and electron microscopy were used to examine CNS tissue from Lewis rats with acute and chronic relapsing EAE.
- Apoptotic macrophages were identified based on distinct morphological criteria, including nuclear condensation and the presence of myelin debris.
- The temporal correlation between macrophage apoptosis and clinical disease progression was assessed.
Main Results:
- Macrophage apoptosis was observed in the CNS of rats with both acute and chronic relapsing EAE.
- Apoptotic macrophages were found in various CNS compartments, including meninges, perivascular spaces, and parenchyma.
- The frequency of apoptotic macrophages peaked during maximal neurological signs and early recovery in acute EAE.
Conclusions:
- Macrophage apoptosis is a significant event in the CNS during EAE.
- Potential triggers for macrophage apoptosis include cytokines, T-cell cytotoxicity, nitric oxide, and glucocorticoids.
- Macrophage apoptosis, alongside T-cell apoptosis, likely contributes to the down-regulation of autoimmune responses in EAE.