The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Activated Microglia Desialylate and Phagocytose Cells via Neuraminidase, Galectin-3, and Mer Tyrosine Kinase
Open accessAbstract
Activated microglia can phagocytose dying, stressed, or excess neurons and synapses via the phagocytic receptor Mer tyrosine kinase (MerTK). Galectin-3 (Gal-3) can cross-link surface glycoproteins by binding galactose residues that are normally hidden below terminal sialic acid residues. Gal-3 was recently reported to opsonize cells via activating MerTK. We found that LPS-activated BV-2 microglia rapidly released Gal-3, which was blocked by calcineurin inhibitors. Gal-3 bound to MerTK on microglia and to stressed PC12 (neuron-like) cells, and it increased microglial phagocytosis of PC12 cells or primary neurons, which was blocked by inhibition of MerTK. LPS-activated microglia exhibited a sialidase activity that desialylated PC12 cells and could be inhibited by Tamiflu, a neuraminidase (sialidase) inhibitor. Sialidase treatment of PC12 cells enabled Gal-3 to bind and opsonize the live cells for phagocytosis by microglia. LPS-induced microglial phagocytosis of PC12 was prevented by small interfering RNA knockdown of Gal-3 in microglia, lactose inhibition of Gal-3 binding, inhibition of neuraminidase with Tamiflu, or inhibition of MerTK by UNC569. LPS-induced phagocytosis of primary neurons by primary microglia was also blocked by inhibition of MerTK. We conclude that activated microglia release Gal-3 and a neuraminidase that desialylates microglial and PC12 surfaces, enabling Gal-3 binding to PC12 cells and their phagocytosis via MerTK. Thus, Gal-3 acts as an opsonin of desialylated surfaces, and inflammatory loss of neurons or synapses may potentially be blocked by inhibiting neuraminidases, Gal-3, or MerTK.
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“This may stem from the BV-2 cells, a transformed microglia cell line with differed morphology compared to microglia directly isolated from the animals,48 which was reported previously.51–53”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [53]
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Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
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Phagocytosis and clearance of apoptotic cells is mediated by MER
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Microglial Phagocytosis of Live Neurons
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Self-citationSecretion of the galectin family of mammalian carbohydrate-binding proteins
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Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
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Fricker, M., Tolkovsky, A. M., Borutaitė, V., Coleman, M. P., & Brown, G. C. (2018) · Physiological Reviews · doi:10.1152/physrev.00011.2017 · Cited by 1,148
Self-citationDysregulation of brain and choroid plexus cell types in severe COVID-19
Yang, A. C., Kern, F., Losada, P. M., Agam, M. R., Maat, C. A., Schmartz, G. P., Fehlmann, T., Stein, J. A., Schaum, N., Lee, D. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03710-0 · Cited by 620
Myers, K. V., Amend, S. R., & Pienta, K. J. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1022-2 · Cited by 490
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365
Boza-Serrano, A., Ruiz, R., Sanchez-Varo, R., García-Revilla, J., Yang, Y., Jimenez-Ferrer, I., Paulus, A., Wennström, M., Vilalta, A., Allendorf, D., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02013-z · Cited by 357
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Metadata
- Authors
- Nomura, K., Vilalta, A., Allendorf, D. H., Hornik, T. C., & Brown, G. C.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Brown, Guy C
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-06
- Volume
- 198
- Issue
- 12
- Pages
- 4792-4801
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC5458330
- OpenAlex
- W2612664982
- Cited by
- 111
- References
- 48
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 14 · 2023: 7 · 2022: 17 · 2021: 17 · 2020: 15 · 2019: 9 · 2018: 7 · 2017: 4
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Medical Research Council (MR/L010593/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- microglia, phagocytosis, galectin-3, MERTK, neuraminidase, sialic acid, desialylation, opsonization, lipopolysaccharide stimulation, PC12 cells, neurons, calcineurin, neuraminidase inhibitors, synaptic loss, neuroinflammation
- MeSH terms
- c-Mer Tyrosine Kinase, Animals, Galactose, Lipopolysaccharides, Macrophages, Neuraminidase, Neurons, Opsonin Proteins, Phagocytosis, Proto-Oncogene Proteins, Pyrazoles, Pyrimidines, PC12 Cells, Microglia, Receptor Protein-Tyrosine Kinases, Galectin 3, Rats, Oseltamivir
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