Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis
| Autor: | Wouter H. Gerritsen, Paul van der Valk, Sandra Amor, Kimberley Ummenthum, Daphne Y.S. Vogel, Priscilla D. A. M. Heijnen, Laura A. N. Peferoen, Christine D. Dijkstra, Marjolein Breur, Regina Peferoen-Baert |
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| Přispěvatelé: | Pathology, Molecular cell biology and Immunology, NCA - Neuroinflamation |
| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Multiple Sclerosis C-C chemokine receptor type 7 Biology Statistics Nonparametric Pathology and Forensic Medicine Proinflammatory cytokine Lesion Cellular and Molecular Neuroscience Antigens CD medicine CXCL10 Humans RNA Messenger Remyelination Myelin Proteolipid Protein Cells Cultured Aged Aged 80 and over Microglia Multiple sclerosis Macrophages Histocompatibility Antigens Class II Brain Cell Differentiation General Medicine Middle Aged medicine.disease Flow Cytometry Cell biology medicine.anatomical_structure Neurology Cytokines Female Neurology (clinical) medicine.symptom Transcriptome Mannose receptor |
| Zdroj: | Journal of Neuropathology and Experimental Neurology, 74(1), 48-63. Lippincott Williams and Wilkins Peferoen, L A N, Vogel, D Y S, Ummenthum, K, Breur, M, Heijnen, P D A M, Gerritsen, W H, Peferoen-Baert, R M B, van der Valk, P, Dijkstra, C D & Amor, S 2015, ' Activation Status of Human Microglia Is Dependent on Lesion Formation Stage and Remyelination in Multiple Sclerosis ', Journal of Neuropathology and Experimental Neurology, vol. 74, no. 1, pp. 48-63 . https://doi.org/10.1097/NEN.0000000000000149 |
| ISSN: | 0022-3069 |
| DOI: | 10.1097/nen.0000000000000149 |
| Popis: | Similar to macrophages, microglia adopt diverse activation states and contribute to repair and tissue damage in multiple sclerosis. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, we show that in vitro M1-polarized (proinflammatory) human adult microglia express the distinctive markers CD74, CD40, CD86, and CCR7, whereas M2 (anti-inflammatory) microglia express mannose receptor and the anti-inflammatory cytokine CCL22. The expression of these markers was assessed in clusters of activated microglia in normal-appearing white matter (preactive lesions) and areas of remyelination, representing reparative multiple sclerosis lesions. We show that activated microglia in preactive and remyelinating lesions express CD74, CD40, CD86, and the M2 markers CCL22 and CD209, but not mannose receptor. To examine whether this intermediate microglia profile is static or dynamic and thus susceptible to changes in the microenvironment, we polarized microglia into M1 or M2 phenotype in vitro and then subsequently treated them with the opposing polarization regimen. These studies revealed that expression of CD40, CXCL10, and mannose receptor is dynamic and that microglia, like macrophages, can switch between M1 and M2 phenotypic profiles. Taken together, our data define the differential activation states of microglia during lesion development in multiple sclerosis-affected CNS tissues and underscore the plasticity of human adult microglia in vitro. |
| Databáze: | OpenAIRE |
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