ArticleJournal of neuroinflammation2014
Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia.
Article in Journal of neuroinflammation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Multimodal Single-Cell Transcriptomic and Chromatin Accessibility Profiling Reveals Monocyte-Derived Macrophage Dynamics Following Ischemic Stroke.International journal of molecular sciences · 2026Article
- Microglia-associated progression of multiple sclerosis: target identification and therapeutic engagement in human in vitro models.Experimental & molecular medicine · 2026Review
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- The development of a direct co-culture-based model for diabetic foot ulcer mimicking inflammation and impaired phagocytosis.In vitro models · 2025Article
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Bridging Retinal and Cerebral Neurodegeneration: A Focus on Crosslinks between Alzheimer-Perusini's Disease and Retinal Dystrophies.Biomedicines · 2023Review
- Human iPSC-derived microglia sense and dampen hyperexcitability of cortical neurons carrying the epilepsy-associated SCN2A-L1342P mutation.bioRxiv : the preprint server for biology · 2023Article
- Assaying Microglia Functions In Vitro.Cells · 2022Review
- Dominant-acting CSF1R variants cause microglial depletion and altered astrocytic phenotype in zebrafish and adult-onset leukodystrophy.Acta neuropathologica · 2022Article
- Lipid metabolism and storage in neuroglia: role in brain development and neurodegenerative diseases.Cell & bioscience · 2022Review
- Human microglial models to study HIV infection and neuropathogenesis: a literature overview and comparative analyses.Journal of neurovirology · 2022Review
- Microglia: Key Players in Retinal Ageing and Neurodegeneration.Frontiers in cellular neuroscience · 2022Review
- Citrullinated myelin induces microglial TNFα and inhibits endogenous repair in the cuprizone model of demyelination.Journal of neuroinflammation · 2021Article
- Multiple sclerosis: why we should focus on both sides of the (auto)antibody.Neural regeneration research · 2021Review
- Review
- Complement-Mediated Microglial Phagocytosis and Pathological Changes in the Development and Degeneration of the Visual System.Frontiers in immunology · 2020Review
- Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes.Nature communications · 2019Article
- The physiology of foamy phagocytes in multiple sclerosis.Acta neuropathologica communications · 2018Review
- Human IgM antibody rHIgM22 promotes phagocytic clearance of myelin debris by microglia.Scientific reports · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors.
methodsMyelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72-hour period. Data were statistically analyzed with the Mann-Whitney U test.
resultsMS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis.
conclusionsMyelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability could be an interesting therapeutic target to prevent or inhibit formation or expansion of MS lesions. Moreover, during aging, microglia enhance their phagocytic capacity for myelin phagocytosis, but myelin reduces its susceptibility for uptake.
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