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Open Access 01-12-2013 | Research

Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status

Authors: Daphne YS Vogel, Elly JF Vereyken, Judith E Glim, Priscilla DAM Heijnen, Martina Moeton, Paul van der Valk, Sandra Amor, Charlotte E Teunissen, Jack van Horssen, Christine D Dijkstra

Published in: Journal of Neuroinflammation | Issue 1/2013

Abstract

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.

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Title: Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status
Authors: Daphne YS Vogel
Elly JF Vereyken
Judith E Glim
Priscilla DAM Heijnen
Martina Moeton
Paul van der Valk
Sandra Amor
Charlotte E Teunissen
Jack van Horssen
Christine D Dijkstra
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-10-35

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Macrophages in inflammatory multiple sclerosis lesions have an intermediate activation status

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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