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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Acknowledgments
This work was funded by Science Foundation Ireland (07/IN.1/B949). RSJ was supported by a Health Research Board-funded structured PhD program in Neuroscience (PhD/2008/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no competing financial interests.
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Jones, R.S., Minogue, A.M., Connor, T.J. et al. Amyloid-β-Induced Astrocytic Phagocytosis is Mediated by CD36, CD47 and RAGE. J Neuroimmune Pharmacol 8, 301–311 (2013). https://doi.org/10.1007/s11481-012-9427-3
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DOI: https://doi.org/10.1007/s11481-012-9427-3