Amyloid-β-Induced Astrocytic Phagocytosis is Mediated by CD36, CD47 and RAGE

• Published in: Journal of neuroimmune pharmacology 2013-03, Vol.8 (1), p.301-311
• Main Authors: Jones, Raasay S., Minogue, Aedín M., Connor, Thomas J., Lynch, Marina A.
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - toxicity; Animals; Animals, Newborn; Astrocytes - drug effects; Biomedical and Life Sciences; Biomedicine; CD11b Antigen - biosynthesis; CD11b Antigen - genetics; CD36 Antigens - physiology; CD47 Antigen - physiology; Cell Biology; Cell Survival - drug effects; Excitatory Amino Acid Transporter 2 - biosynthesis; Excitatory Amino Acid Transporter 2 - genetics; Flow Cytometry; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Glial Fibrillary Acidic Protein - biosynthesis; Glial Fibrillary Acidic Protein - genetics; Immunology; L-Lactate Dehydrogenase - metabolism; Microglia - drug effects; Microspheres; Neurosciences; Original Article; Phagocytosis - drug effects; Pharmacology/Toxicology; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Immunologic - physiology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Virology
• ISSN: 1557-1890; 1557-1904
• DOI: 10.1007/s11481-012-9427-3

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.