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Brain Advance Access published online on December 19, 2005
Brain, doi:10.1093/brain/awh707
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© The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 1, 2005
Revised October 11, 2005
Accepted October 27, 2005

Article

Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis

Leonie A. Boven 1 *, Marjan Van Meurs 1, Marloes Van Zwam 1, Annet Wierenga-Wolf 1, Rogier Q. Hintzen 2, Rolf G. Boot 3, Johannes M. Aerts 3, Sandra Amor 4, Edward E. Nieuwenhuis 5 *, and Jon D. Laman 1 *

1 Department of Immunology, part of the multiple sclerosis Centre ErasMS, Rotterdam, The Netherlands
2 Department of Neurology, part of the multiple sclerosis Centre ErasMS, Rotterdam, The Netherlands
3 Department of Medical Biochemistry, Academic Medical Center Amsterdam, The Netherlands
4 Biomedical Primate Research Center, part of the multiple sclerosis Centre ErasMS, Rijswijk, The Netherlands
5 Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands

* To whom correspondence should be addressed.
Leonie A. Boven, E-mail: l.boven{at}erasmusmc.nl


  Abstract

Multiple sclerosis lesion activity concurs with the extent of inflammation, demyelination and axonal suffering. Pro-inflammatory myeloid cells contribute to lesion development, but the self-limiting nature of lesions implies as yet unidentified anti-inflammatory mechanisms. We addressed the hypothesis that myelin ingestion by myeloid cells induces a foamy appearance and confers anti-inflammatory function. First, we show that myelin-containing foam cells in multiple sclerosis lesions consistently express a series of anti-inflammatory molecules while lacking pro-inflammatory cytokines. Second, unique location-dependent cytokine and membrane receptor expression profiles imply functional specialization allowing for differential responses to micro-environmental cues. A novel human in vitro model of foamy macrophages functionally confirmed that myelin ingestion induces an anti-inflammatory programme. Foamy macrophages are unable to respond to prototypical inflammatory stimuli but do express molecules involved in suppression of inflammation. These findings provide novel insights into the mechanisms of lesion control and may open new roads to intervention.

Keywords: autoimmunity; brain; chemokines; cytokines; inflammation.
*These authors contributed equally to this work.
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