title: Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells.
abstract: Primary microglial cultures prepared from newborn mice showed the production and release of the third component of complement (C3). Newly synthesized [35S]methionine-labelled C3 was purified by immunoprecipitation using anti-C3-antibody. C3 was detected by SDS-PAGE and fluoroaraphy of the immunoprecipitated protein from cell lysates as a 195 kDa band, and from the supernatants of cultures as two major bands corresponding to the C3 alpha-chain (125 kDa) and beta-chain (75 kDa), consistent with known C3 characteristics. Increased biosynthesis of C3 was elicited by endotoxin lipopolysaccharide (LPS). Further, the synthesis of C3 was increased 5-10-fold in response to various synthetic peptides corresponding to the amyloid beta/A4 protein, which is the main constituent of extracellular amyloid deposits in Alzheimer's disease (AD). The increased synthesis of C3 was shown to be dose dependent at concentrations of beta/A4 peptide ranging from 10 micrograms/ml to 50 micrograms/ml. These results suggest that complement components found previously in amyloid deposits may be partly derived from reactive microglia preferentially associated with senile plaques in AD brain.
authors.affiliation: Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Haga
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Ishii
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis*; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007202:Indicators and Reagents; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011233:Precipitin Tests; D013268:Stimulation, Chemical
chemical_list: D016229:Amyloid beta-Peptides; D003176:Complement C3; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor