title: Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis.
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.
authors.affiliation: Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands. l.boven@erasmusmc.nl
authors.forename: Leonie A
authors.initials: LA
authors.lastname: Boven
authors.forename: Marjan
authors.initials: M
authors.lastname: Van Meurs
authors.forename: Marloes
authors.initials: M
authors.lastname: Van Zwam
authors.forename: Annet
authors.initials: A
authors.lastname: Wierenga-Wolf
authors.forename: Rogier Q
authors.initials: RQ
authors.lastname: Hintzen
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Aerts
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.forename: Edward E
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
mesh_terms: 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
chemical_list: 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