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In vitro Quantitative Imaging Assay for Phagocytosis of Dead Neuroblastoma Cells by iPSC-Macrophages
Published on: February 14, 2021
Macrophages and neurodegeneration
Jerome J A Hendriks1, Charlotte E Teunissen, Helga E de Vries
1Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Abstract:
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Demyelination is a classical feature of MS lesions, and neurological deficits are often ascribed to the reduced signal conduction by demyelinated axons. However, recent studies emphasize that axonal loss is an important factor in MS pathogenesis and disease progression. Axonal loss is found in association with cellular infiltrates in MS lesions. In this review, we discuss the possible contribution of the innate immune system in this process. In particular, we describe how infiltrated macrophages may contribute to axonal loss in MS and in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. An overview is given of the possible effects of mediators, which are produced by activated macrophages, such as such as pro-inflammatory cytokines, free radicals, glutamate and metalloproteases, on axonal integrity. We conclude that infiltrated macrophages, which are activated to produce pro-inflammatory mediators, may be interesting targets for therapeutic approaches aimed to prevent or reduce axonal loss during exacerbation of inflammation. Interference with the process of infiltration and migration of monocytes across the blood-brain barrier is one of the possibilities to reduce the damage by activated macrophages.
Insights
Macrophages contribute to axonal loss in multiple sclerosis (MS) by releasing damaging mediators. Targeting these activated immune cells may prevent further neurological damage in MS patients.
Area of Science:
- Neuroimmunology
- Pathology of Multiple Sclerosis
Background:
- Multiple sclerosis (MS) is a chronic CNS inflammatory disease characterized by demyelination.
- Axonal loss, alongside demyelination, is increasingly recognized as a key driver of MS pathogenesis and progression.
- Axonal damage in MS lesions is associated with the presence of infiltrating immune cells.
Purpose of the Study:
- To review the role of the innate immune system, specifically macrophages, in causing axonal loss in MS.
- To examine the mechanisms by which activated macrophages contribute to axonal damage.
- To identify potential therapeutic targets for preventing axonal loss in MS.
Main Methods:
- Review of existing literature on MS, experimental autoimmune encephalomyelitis (EAE), and innate immunity.
- Analysis of the effects of macrophage-derived mediators on axonal integrity.
- Discussion of therapeutic strategies targeting macrophage infiltration and activation.
Main Results:
- Infiltrated macrophages in MS lesions contribute to axonal loss.
- Activated macrophages release mediators like pro-inflammatory cytokines, free radicals, glutamate, and metalloproteases that harm axons.
- Experimental autoimmune encephalomyelitis (EAE) models support the role of macrophages in axonal damage.
Conclusions:
- Activated macrophages are significant contributors to axonal loss in multiple sclerosis.
- Targeting activated macrophages and their mediators offers a promising therapeutic avenue to reduce axonal damage during MS exacerbations.
- Inhibiting monocyte infiltration across the blood-brain barrier could mitigate macrophage-induced axonal injury.
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