Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis.
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.
Boven
Leonie A
LA
Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands. l.boven@erasmusmc.nl
Van Meurs
Marjan
M
Van Zwam
Marloes
M
Wierenga-Wolf
Annet
A
Hintzen
Rogier Q
RQ
Boot
Rolf G
RG
Aerts
Johannes M
JM
Amor
Sandra
S
Nieuwenhuis
Edward E
EE
Laman
Jon D
JD
D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis
D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4