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Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages

التفاصيل البيبلوغرافية
العنوان: Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages
المؤلفون: Arend H. Sikkema, Josephine M. J. Stoffels, Peng Wang, Frederike J. Basedow, Robbert Bulsink, Jeffrey J. Bajramovic, Wia Baron
المصدر: Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-17 (2018)
بيانات النشر: BMC, 2018.
سنة النشر: 2018
المجموعة: LCC:Neurology. Diseases of the nervous system
مصطلحات موضوعية: Fibronectin, Macrophage, Microglia, Multiple sclerosis, Neurology. Diseases of the nervous system, RC346-429
الوصف: Abstract 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-γ (IFNγ) 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 IFNγ 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 may clarify the induction of both pro-inflammatory and anti-inflammatory features in macrophages cultured on fibronectin aggregate, but not plasma fibronectin coatings. Conclusions Macrophages and microglia grown on aggregated fibronectin coatings adopt a distinct phenotype compared to plasma fibronectin coatings, showing pro-inflammatory and anti-inflammatory features. Therefore, the pathological fibronectin aggregates in MS lesions may impair remyelination by promoting and/or retaining several classically activated phenotypic features in microglia and macrophages.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1742-2094
Relation: http://link.springer.com/article/10.1186/s12974-018-1238-x; https://doaj.org/toc/1742-2094
DOI: 10.1186/s12974-018-1238-x
URL الوصول: https://doaj.org/article/b5ac1e2b50d540f0b9784401534f4c25
رقم الأكسشن: edsdoj.b5ac1e2b50d540f0b9784401534f4c25
قاعدة البيانات: Directory of Open Access Journals
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