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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.9.4350 · Cited by 53,218
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311
Greene, L., & Tischler, A. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.7.2424 · Cited by 5,566
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377
Phagocytosis and clearance of apoptotic cells is mediated by MER
Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., & Matsushima, G. K. (2001) · Nature · doi:10.1038/35075603 · Cited by 1,215
Immortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,076
Microglial Phagocytosis of Live Neurons
Brown, G. C., & Neher, J. J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3710 · Cited by 853
Self-citationSecretion of the galectin family of mammalian carbohydrate-binding proteins
Hughes, R. C. (1999) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(99)00177-4 · Cited by 652
Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Sierra, A., Abiega, O., Shahraz, A., & Neumann, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00006 · Cited by 574
Hirabayashi, J., & Kasai, K.-I. (1993) · Glycobiology · doi:10.1093/glycob/3.4.297 · Cited by 529
Ho, M., & Springer, T. A. (1982) · The Journal of Immunology · doi:10.4049/jimmunol.128.3.1221 · Cited by 426
Liu, F., Hsu, D. K., Zuberi, R. I., Kuwabara, I., Chi, E. Y., & Henderson, W. R. (1995) · Europe PMC (PubMed Central) · Cited by 403
Mammalian sialidases: Physiological and pathological roles in cellular functions
Miyagi, T., & Yamaguchi, K. (2012) · Glycobiology · doi:10.1093/glycob/cws057 · Cited by 390
Inhibition of Microglial Phagocytosis Is Sufficient To Prevent Inflammatory Neuronal Death
Neher, J. J., Neniskyte, U., Zhao, J.-W., Bal-Price, A., Tolkovsky, A. M., & Brown, G. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003600 · Cited by 373
Self-citationBurguillos, M. A., Svensson, M., Schulte, T., Boza-Serrano, A., Garcia-Quintanilla, A., Kavanagh, E., Santiago, M., Viceconte, N., Oliva-Martin, M. J., Osman, A. M., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.02.012 · Cited by 365
Phagocytosis executes delayed neuronal death after focal brain ischemia
Neher, J. J., Emmrich, J., Fricker, M., Mander, P. K., Théry, C., & Brown, G. C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308679110 · Cited by 357
Self-citationEaten alive! Cell death by primary phagocytosis: ‘phagoptosis’
Brown, G. C., & Neher, J. J. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.05.002 · Cited by 331
Self-citationBrown, G. C., & Vilalta, A. (2015) · Brain Research · doi:10.1016/j.brainres.2015.08.031 · Cited by 322
Self-citationNeumann, J. H. L., Sauerzweig, S., Rönicke, R., Gunzer, F., Dinkel, K., Ullrich, O., Gunzer, M., & Reymann, K. G. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0060-08.2008 · Cited by 261
Microglia function during brain development: New insights from animal models
Bilimoria, P. M., & Stevens, B. (2015) · Brain Research · doi:10.1016/j.brainres.2014.11.032 · Cited by 237
Amith, S. R., Jayanth, P., Franchuk, S. L., Finlay, T. M., Seyrantepe, V., Beyaert, R., Pshezhetsky, A. V., & Szewczuk, M. R. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.09.038 · Cited by 200
Galectin-3 is a new MerTK-specific eat-me signal
Caberoy, N. B., Alvarado, G., Bigcas, J., & Li, W. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.22955 · Cited by 176
Emerging Role of α2,6-Sialic Acid as a Negative Regulator of Galectin Binding and Function
Zhuo, Y., & Bellis, S. L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.191429 · Cited by 174
Grommes, C., Lee, C. Y. D., Wilkinson, B. L., Jiang, Q., Koenigsknecht-Talboo, J. L., Varnum, B., & Landreth, G. E. (2008) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-007-9090-2 · Cited by 162
Yip, P. K., Carrillo-Jiménez, A., King, P., Vilalta, A., Nomura, K., Chau, C. C. C., Scott-Egerton, A. M., Liu, Z., Shetty, A. J., Tremoleda, J. L., et al. (2017) · Scientific Reports · doi:10.1038/srep41689 · Cited by 143
Self-citationGalectin-3 contributes to neonatal hypoxic–ischemic brain injury
Doverhag, C., Hedtjärn, M., Poirier, F., Mallard, C. E., Hagberg, H., Karlsson, A., & Sävman, K. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.12.024 · Cited by 140
Fricker, M., Oliva-Martín, M. J., & Brown, G. C. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-196 · Cited by 137
Self-citationLinnartz, B., Kopatz, J., Tenner, A. J., & Neumann, H. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3830-11.2012 · Cited by 134
Galectin-3 mediates post-ischemic tissue remodeling
Yan, Y., Lang, B. T., Vemuganti, R., & Dempsey, R. J. (2009) · Brain Research · doi:10.1016/j.brainres.2009.06.073 · Cited by 130
Eat‐me signals: Keys to molecular phagocyte biology and “Appetite” control
Li, W. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22815 · Cited by 117
Rotshenker, S. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9186-7 · Cited by 111
Li, X., Wang, J., Fang, B., Tan, W., & Ma, H. (2014) · Molecular Brain · doi:10.1186/1756-6606-7-28 · Cited by 102
Claude, J., Linnartz-Gerlach, B., Kudin, A. P., Kunz, W. S., & Neumann, H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2211-13.2013 · Cited by 98
Where catabolism meets signalling: neuraminidase 1 as a modulator of cell receptors
Pshezhetsky, A. V., & Hinek, A. (2011) · Glycoconjugate Journal · doi:10.1007/s10719-011-9350-5 · Cited by 90
Nuclear transport of galectin-3 and its therapeutic implications
Funasaka, T., Raz, A., & Nangia‐Makker, P. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.03.004 · Cited by 87
Siglec‐h on activated microglia for recognition and engulfment of glioma cells
Kopatz, J., Beutner, C., Welle, K., Bodea, L., Reinhardt, J., Claude, J., Linnartz‐Gerlach, B., & Neumann, H. (2013) · Glia · doi:10.1002/glia.22501 · Cited by 76
Christoph, S., DeRyckere, D., Schlegel, J., Frazer, J. K., Batchelor, L. A., Trakhimets, A. Y., Sather, S., Hunter, D. M., Cummings, C. T., Liu, J., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0040 · Cited by 72
Feng, C., Zhang, L., Almulki, L., Faez, S., Whitford, M., Hafezi‐Moghadam, A., & Cross, A. S. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.1210708 · Cited by 65
Jennings, C., Kusler, B., & Jones, P. P. (2009) · Innate Immunity · doi:10.1177/1753425908100928 · Cited by 59
Galectins and Neuroinflammation
Chen, H.-L., Liao, F., Lin, T., & Liu, F. (2014) · Advances in neurobiology · doi:10.1007/978-1-4939-1154-7_24 · Cited by 58
Hornik, T. C., Neniškytė, U., & Brown, G. C. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12477 · Cited by 58
Self-citationSatoh, K., Niwa, M., Goda, W., Bình, N. H., Nakashima, M., Takamatsu, M., & Hara, A. (2011) · Brain Research · doi:10.1016/j.brainres.2011.01.049 · Cited by 53
Pereira, M. E. A. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90206-5 · Cited by 43
Wang, C., Liu, X., Huang, K., Yin, S.-B., Wei, J., Hu, Y., Gu, Y., & Zheng, G. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13611 · Cited by 28
Sweet kiss of dying cell: Sialidase activity on apoptotic cell is able to act toward its neighbors
Shkandina, T., i, M. H., & Bilyy, R. O. (2012) · Autoimmunity · doi:10.3109/08916934.2012.719951 · Cited by 17
Nomura, K., Lee, M., Banks, C., Lee, G. L., & MORRIS, B. J. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.05.045 · Cited by 15
Self-citation
Cited by
Sorted by citations
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
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
