Related Experiment Video
Updated: Apr 27, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Differential roles of microglia and monocytes in the inflamed central nervous system
Ryo Yamasaki1, Haiyan Lu1, Oleg Butovsky2
1Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute; Department of Quantitative Health Sciences; and Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH 44106.
Abstract:
In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.
Insights
Monocyte-derived macrophages initiate demyelination in autoimmune diseases like multiple sclerosis, while microglia clear debris. Differentiating these macrophage origins offers new therapeutic targets for inflammatory conditions.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathology
Background:
- Macrophages are key players in inflammatory demyelination in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
- Distinguishing between infiltrating monocytes and resident microglia origins of macrophages is crucial for understanding disease mechanisms.
- Current understanding of tissue injury during inflammatory demyelination remains incomplete.
Purpose of the Study:
- To differentiate the origins and functions of effector macrophages in autoimmune demyelination.
- To investigate the roles of monocyte-derived macrophages versus microglia in experimental autoimmune encephalomyelitis.
Main Methods:
- Serial block-face scanning electron microscopy (SBF-SEM) was used to visualize macrophage origins.
- Gene expression profiling was employed to analyze macrophage characteristics.
Main Results:
- Monocyte-derived macrophages were found at nodes of Ranvier, initiating demyelination.
- Microglia were observed to be involved in debris clearance.
- Gene expression revealed monocyte-derived macrophages as phagocytic and inflammatory, while microglia exhibited suppressed metabolism at disease onset.
Conclusions:
- Monocyte-derived macrophages are the primary drivers of demyelination.
- Microglia play a distinct role in debris clearance and exhibit unique metabolic profiles.
- Identifying macrophage origins provides novel therapeutic strategies for MS and other inflammatory diseases.
Related Concept Videos
01:12Chronic Inflammation: Introduction
01:38Inflammation
01:15Differentiation of Common Myeloid Progenitor Cells
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...