Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status
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Updated: May 13, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
Daphne Y S Vogel1, Elly J F Vereyken, Judith E Glim
1Department of Molecular Cell Biology and Immunology, VU University Medical Center, Van der Boechhorststraat 7, BT Amsterdam, 1081, The Netherlands.
Background:
Macrophages play a dual role in multiple sclerosis (MS) pathology. They can exert neuroprotective and growth promoting effects but also contribute to tissue damage by production of inflammatory mediators. The effector function of macrophages is determined by the way they are activated. Stimulation of monocyte-derived macrophages in vitro with interferon-γ and lipopolysaccharide results in classically activated (CA/M1) macrophages, and activation with interleukin 4 induces alternatively activated (AA/M2) macrophages.
Methods:
For this study, the expression of a panel of typical M1 and M2 markers on human monocyte derived M1 and M2 macrophages was analyzed using flow cytometry. This revealed that CD40 and mannose receptor (MR) were the most distinctive markers for human M1 and M2 macrophages, respectively. Using a panel of M1 and M2 markers we next examined the activation status of macrophages/microglia in MS lesions, normal appearing white matter and healthy control samples.
Results:
Our data show that M1 markers, including CD40, CD86, CD64 and CD32 were abundantly expressed by microglia in normal appearing white matter and by activated microglia and macrophages throughout active demyelinating MS lesions. M2 markers, such as MR and CD163 were expressed by myelin-laden macrophages in active lesions and perivascular macrophages. Double staining with anti-CD40 and anti-MR revealed that approximately 70% of the CD40-positive macrophages in MS lesions also expressed MR, indicating that the majority of infiltrating macrophages and activated microglial cells display an intermediate activation status.
Conclusions:
Our findings show that, although macrophages in active MS lesions predominantly display M1 characteristics, a major subset of macrophages have an intermediate activation status.
Insights
Macrophages in multiple sclerosis (MS) lesions are predominantly activated (M1 type), but many also show intermediate activation. This suggests a complex role for these immune cells in MS pathology, influencing disease progression and potential therapeutic targets.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathology
Background:
- Macrophages exhibit dual roles in multiple sclerosis (MS) pathology, with potential for neuroprotection or tissue damage.
- Macrophage activation states, classically activated (M1) and alternatively activated (M2), dictate their functional outcomes.
- Understanding macrophage activation in MS is crucial for deciphering disease mechanisms.
Purpose of the Study:
- To investigate the activation status of macrophages and microglia within multiple sclerosis (MS) lesions.
- To identify reliable markers for distinguishing M1 and M2 macrophage phenotypes in human samples.
- To characterize the spectrum of macrophage activation in different MS pathological contexts.
Main Methods:
- Flow cytometry was used to analyze the expression of M1 and M2 markers on human monocyte-derived macrophages.
- CD40 and mannose receptor (MR) were identified as key distinguishing markers for M1 and M2 macrophages, respectively.
- The expression of M1/M2 markers was assessed in macrophages/microglia from MS lesions, normal-appearing white matter, and healthy controls.
Main Results:
- M1 markers (CD40, CD86, CD64, CD32) were highly expressed on microglia in normal-appearing white matter and in active MS lesions.
- M2 markers (MR, CD163) were found on myelin-laden and perivascular macrophages within active MS lesions.
- Approximately 70% of CD40-positive macrophages in MS lesions co-expressed MR, indicating an intermediate activation status.
Conclusions:
- Macrophages in active MS lesions primarily exhibit M1 characteristics.
- A significant subset of macrophages within MS lesions displays an intermediate activation phenotype.
- These findings highlight the complexity of macrophage polarization in MS and its implications for disease pathogenesis.
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