title: Complement component C1q modulates the phagocytosis of Abeta by microglia.
abstract: Recent studies showing that microglia internalize the amyloid beta-peptide (Abeta) suggest that these cells have the potential for clearing Abeta deposits in Alzheimer's disease, and mechanisms that regulate the removal of Abeta may therefore be of clinical interest. Previous studies from this laboratory showing that C1q enhances phagocytosis of cellular targets by rat microglia prompted the current investigations characterizing the effects of C1q on microglial phagocytosis of Abeta. Microglia were shown to phagocytose Abeta1-42, in agreement with observations of other investigators. Uptake of Abeta1-42 was observed for concentrations of 5-50 microM, and phagocytosis of peptides containing (14)C or fluorescein (FM) labels was not affected by the interaction of microglia with C1q-coated surfaces. However, inclusion of C1q (125 nM-1.4 microM) in solutions of 50 microM Abeta1-42 inhibited the uptake of (14)C-Abeta1-42 and FM-Abeta1-42, suggesting that C1q blocks the interaction of Abeta with microglia. Uptake of Abeta was partially blocked by the scavenger receptor ligands polyinosinic acid and maleylated BSA. Inhibition of Abeta uptake by C1q may contribute to the accumulation of fibrillar, C1q-containing plaques that occurs in parallel with disease progression. These data suggest that mechanisms which interfere with the binding of C1q to Abeta may be of therapeutic value both through inhibition of the inflammatory events resulting from complement activation and via altered access of Abeta sites necessary for ingestion by microglia.
authors.affiliation: Department of Molecular Biology, University of California, Irvine, California, 92697, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Webster
authors.forename: A J
authors.initials: AJ
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Margol
authors.forename: W
authors.initials: W
authors.lastname: Garzon-Rodriguez
authors.forename: C G
authors.initials: CG
authors.lastname: Glabe
authors.forename: A J
authors.initials: AJ
authors.lastname: Tenner
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000276:immunology; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D015922:Complement C1q / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008565:Membrane Proteins; D017628:Microglia / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D010446:Peptide Fragments / Q000032:analysis / Q000493:pharmacokinetics*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D017434:Protein Structure, Tertiary; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry / Q000502:physiology; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D002250:Carbon Radioisotopes; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C075222:amyloid beta-protein (1-42); D015922:Complement C1q