Journal Article

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

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

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 2, pages 517-526
Published in print February 2006 | ISSN: 0006-8950
Published online December 2005 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awh707
Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis

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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; MOG = myelin oligodendrocyte glycoprotein; NAWM = normal appearing white matter; ORO = oil red O; PGES = prostaglandin E2 synthase

Journal Article.  5865 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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