دورية أكاديمية
Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages
| العنوان: | Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages |
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| المؤلفون: | Sikkema, Arend H., Stoffels, Josephine M. J., Wang, Peng, Basedow, Frederike J., Bulsink, Robbert, Bajramovic, Jeffrey J., Baron, Wia |
| المصدر: | Sikkema , A H , Stoffels , J M J , Wang , P , Basedow , F J , Bulsink , R , Bajramovic , J J & Baron , W 2018 , ' Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages ' , Journal of neuroinflammation , vol. 15 , no. 218 , 218 . https://doi.org/10.1186/s12974-018-1238-xTest |
| سنة النشر: | 2018 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Fibronectin, Macrophage, Microglia, Multiple sclerosis, MULTIPLE-SCLEROSIS LESIONS, CENTRAL-NERVOUS-SYSTEM, EXTRACELLULAR-MATRIX, CNS REMYELINATION, MICROGLIAL CELLS, GROWTH-FACTOR, UP-REGULATION, NITRIC-OXIDE, DIFFERENTIATION, EXPRESSION |
| الوصف: | Background: Means to promote endogenous remyelination in multiple sclerosis (MS) benefit from insights into the role of inhibitory molecules that preclude remyelination. Fibronectin assembles into aggregates in MS, which impair oligodendrocyte differentiation and remyelination. Microglia and macrophages are required for complete remyelination and normally switch from a pro-inflammatory classical phenotype upon demyelination to a supportive alternative phenotype during remyelination. Here, we investigated the role of fibronectin aggregates in modulating microglia and macrophage behavior and phenotypes. Methods: Bone marrow-derived macrophages and microglia from newborn rats were exposed to (a) plasma fibronectin coatings; (b) coatings of deoxycholate-insoluble fibronectin aggregates; (c) interferon-gamma (IFN gamma) treatment, as an inducer of the pro-inflammatory classically activated phenotype; (d) interleukin-4 (IL-4) treatment, to promote the pro-regenerative anti-inflammatory alternatively activated phenotype; or (e) left unstimulated on uncoated plastic. To examine the in vitro effects of the different stimulations on cell behavior and phenotype, proliferation, phagocytosis, morphology, and pro- and anti-inflammatory features were assessed. Results: In line with a classically activated phenotype, exposure of microglia and macrophages to both plasma fibronectin and fibronectin aggregates induced an amoeboid morphology and stimulated phagocytosis by macrophages. Furthermore, as observed upon IFN gamma. treatment, coatings of aggregated, but not plasma fibronectin, promoted nitric oxide release by microglia and macrophages. Remarkably, fibronectin aggregates induced nitric oxide release in an integrin-independent manner. In addition, fibronectin aggregates, but not plasma fibronectin, increased the expression of arginase-1, similarly as observed upon treatment with IL-4. Proteomic analysis revealed that aggregates of fibronectin act as a scaffold for other proteins, including Hsp70 and thrombospondin-1, which ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/ab6c4c8b-67b3-4fe0-a815-f3cdaa6efd24Test |
| DOI: | 10.1186/s12974-018-1238-x |
| الإتاحة: | https://doi.org/10.1186/s12974-018-1238-xTest https://hdl.handle.net/11370/ab6c4c8b-67b3-4fe0-a815-f3cdaa6efd24Test https://research.rug.nl/en/publications/ab6c4c8b-67b3-4fe0-a815-f3cdaa6efd24Test https://pure.rug.nl/ws/files/63902869/s12974_018_1238_x_1_.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.11903BC0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12974-018-1238-x |
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