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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/16494

Title: Myelin alters the inflammatory phenotype of macrophages by activating PPARs
Authors: BOGIE, Jeroen
Van Horssen, Jack
Hellings, Niels
Stinissen, Piet
Hendriks, J. J. A.
Nijland, Philip G.
Zelcer, Noam
Issue Date: 2013
Citation: Acta Neuropathologica Communications, 1 (43), p. 1-13
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.
URI: http://hdl.handle.net/1942/16494
Link to publication: http://www.actaneurocomms.org/content/1/August/2013
DOI: 10.1186/2051-5960-1-43
ISSN: 0001-6322
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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