Antibody-mediated phagocytosis of the amyloid beta-peptide in microglia is differentially modulated by C1q

• Published in: The Journal of immunology (1950) 2001-06, Vol.166 (12), p.7496-7503
• Main Authors: Webster, S D, Galvan, M D, Ferran, E, Garzon-Rodriguez, W, Glabe, C G, Tenner, A J
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - immunology; Amyloid beta-Peptides - metabolism; Animals; Antibodies - metabolism; Antibodies - physiology; Antigen-Antibody Complex - metabolism; Carrier Proteins; Cell Line; Cells, Cultured; Centrifugation; Collagen - metabolism; Collagen - physiology; Complement C1q - immunology; Complement C1q - metabolism; Complement C1q - physiology; complement component C1q; Ferritins - metabolism; Ferritins - physiology; Flow Cytometry; Humans; Hyaluronan Receptors; Ligands; Membrane Glycoproteins; Membrane Proteins; Microglia - immunology; Microglia - metabolism; Mitochondrial Proteins; Peptide Fragments - immunology; Peptide Fragments - metabolism; Phagocytosis - immunology; Poly I - metabolism; Poly I - pharmacology; Polysaccharides - metabolism; Polysaccharides - pharmacology; Rats; Receptors, Complement - metabolism; Receptors, Immunologic - metabolism; Receptors, Lipoprotein; Receptors, Scavenger; Scavenger Receptors, Class B; Serum Albumin - metabolism; Serum Albumin - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.12.7496

Microglial ingestion of the amyloid beta-peptide (Abeta) has been viewed as a therapeutic target in Alzheimer's disease, in that approaches that enhance clearance of Abeta relative to its production are predicted to result in decreased senile plaque formation, a proposed contributor to neuropathology. In vitro, scavenger receptors mediate ingestion of fibrillar Abeta (fAbeta) by microglia. However, the finding that cerebral amyloid deposition in a transgenic mouse model of Alzheimer's disease was diminished by inoculation with synthetic Abeta has suggested a possible therapeutic role for anti-Abeta Ab-mediated phagocytosis. Microglia also express C1qR(P), a receptor for complement protein C1q, ligation of which in vitro enhances phagocytosis of immune complexes formed with IgG levels below that required for optimal FcR-mediated phagocytosis. The data presented here demonstrate FcR-dependent ingestion of Abeta-anti-Abeta complexes (IgG-fAbeta) by microglia that is a function of the amount of Ab used to form immune complexes. In addition, C1q incorporated into IgG-fAbeta enhanced microglial uptake of these complexes when they contained suboptimal levels of anti-Abeta Ab. Mannose binding lectin and lung surfactant protein A, other ligands of C1qR(P), also enhanced ingestion of suboptimally opsonized IgG-fAbeta, whereas control proteins did not. Our data suggest that C1qR(P)-mediated events may promote efficient ingestion of Abeta at low Ab titers, and this may be beneficial in paradigms that seek to clear amyloid via FcR-mediated mechanisms by minimizing the potential for destructive Ab-induced complement-mediated processes.