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Amyloid-β-Induced Astrocytic Phagocytosis is Mediated by CD36, CD47 and RAGE
Abstract
Astrocytes, the most numerous glial cell in the brain, have multiple functions and are key to maintenance of homeostasis in the central nervous system. Microglia are the resident immunocompetent cells in the brain and share several functions with macrophages, including their phagocytic ability. Indeed microglia are the resident phagocytes in the brain and express numerous cell surface proteins which act to enable receptor-mediated phagocytosis. However recent evidence suggests that astrocytes express some genes which permit phagocytosis of phosphatidylserine-decorated cells and this probably explains sporadic reports in the literature which suggest that astrocytes become phagocytic following brain trauma. Here we examined the potential of astrocytes to phagocytose fluorescently-labelled latex beads and amyloid-β (Aβ) and report that they competently engulf both in a manner that relies on actin polymerization since it was inhibited by cytochalasin D. The data indicate that incubation of cultured astrocytes or microglia with Aβ increased phagocytosis and markers of activation of both cell types. Aβ was found to markedly increase expression of the putative Aβ-binding receptors CD36 and CD47 in astrocytes, while it decreased expression of the receptor for advanced glycation endproducts (RAGE). It is demonstrated that blocking these receptors using a neutralizing antibody attenuated Aβ-induced phagocytosis of latex beads by astrocytes. Interestingly blocking these receptors also decreased uptake of beads even in the absence of Aβ. Here we demonstrate that astrocytes are competent phagocytes and are capable of engulfing Aβ.
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“Blocking receptors including CD36, CD47, and RAGE with neutralizing antibodies can attenuate astrocytic phagocytosis of Aβ, implicating they are putative Aβ receptors in astrocytes [407].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [407]
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Cited by
Sorted by citations
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
“Blocking receptors including CD36, CD47, and RAGE with neutralizing antibodies can attenuate astrocytic phagocytosis of Aβ, implicating they are putative Aβ receptors in astrocytes [407].”
BackgroundAstrocyte roles in traumatic brain injury
Burda, J. E., Bernstein, A. M., & Sofroniew, M. V. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.03.020 · Cited by 791
“Intriguingly, amyloid-β mediated activation of astrocyte RAGE stimulates astrocytes themselves to become phagocytic and engulf extracellular amyloid-β (Jones et al., 2013), possibly implicating reactive astrocytes in the clearance of neuro- and gliotoxic amyloid protein after injury.”
BackgroundLian, H., Litvinchuk, A., Chiang, A. C.-A., Aithmitti, N., Jankowsky, J. L., & Zheng, H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2117-15.2016 · Cited by 597
“Microglial uptake of both artificial substrates such as fluorescent latex beads and more realistic targets such as synthetic A 42 aggregates is accomplished through phagocytosis (Koenigsknecht and Landreth, 2004; Smith et al., 2010; Jones et al., 2013).”
BackgroundGonzález-Reyes, R. E., Nava-Mesa, M. O., Vargas-Sánchez, K., Ariza-Salamanca, D. F., & Mora-Muñoz, L. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00427 · Cited by 541
“Furthermore, astrocytes have been reported to adopt a phagocytic profile capable of engulfing A β , mediated by CD36, CD47, and RAGE receptors (Jones et al., 2013).”
BackgroundMechanisms of Aβ Clearance and Degradation by Glial Cells
Ries, M., & Sastre, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00160 · Cited by 527
“Although RAGE receptors have been mainly involved in mediating the inflammatory cascade in activated microglia (Solito and Sastre, 2012), their role in Aβ phagocytosis in astrocytes has been recently demonstrated when blocking these receptors with specific antibodies (Jones et al., 2013).”
Background
Metadata
- Authors
- Jones, R. S., Minogue, A. M., Connor, T. J., & Lynch, M. A.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Minogue, Aedín M.
- ORCID
- Lynch, Marina A.
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2012-12-14
- Volume
- 8
- Issue
- 1
- Pages
- 301-311
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- OpenAlex
- W2036955747
- Cited by
- 147
- References
- 46
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 6 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 7 · 2014: 15 · 2013: 2
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyloid-beta, astrocytes, phagocytosis, CD36, CD47, RAGE, actin polymerization, microglia, receptor-mediated phagocytosis, receptor antagonists, neuroinflammation
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Animals, Newborn, Astrocytes, Cell Survival, Flow Cytometry, Fluorescent Dyes, Glial Fibrillary Acidic Protein, L-Lactate Dehydrogenase, Microspheres, Phagocytosis, Receptors, Immunologic, RNA, Messenger, Amyloid beta-Peptides, Fluorescein-5-isothiocyanate, Rats, Wistar, Microglia, CD36 Antigens, Excitatory Amino Acid Transporter 2, CD11b Antigen, Rats, CD47 Antigen
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