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Open Access 01-12-2013 | Research

Myelin alters the inflammatory phenotype of macrophages by activating PPARs

Authors: Jeroen FJ Bogie, Winde Jorissen, Jo Mailleux, Philip G Nijland, Noam Zelcer, Tim Vanmierlo, Jack Van Horssen, Piet Stinissen, Niels Hellings, Jerome JA Hendriks

Published in: Acta Neuropathologica Communications | Issue 1/2013

Abstract

Background

Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear.

Results

We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPARβ/δ is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPARβ/δ in macrophages in the human brain.

Conclusion

Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPARβ/δ activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics.

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Title: Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Authors: Jeroen FJ Bogie
Winde Jorissen
Jo Mailleux
Philip G Nijland
Noam Zelcer
Tim Vanmierlo
Jack Van Horssen
Piet Stinissen
Niels Hellings
Jerome JA Hendriks
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-1-43

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Myelin alters the inflammatory phenotype of macrophages by activating PPARs

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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