Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells.
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.
Haga
S
S
Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, Japan.
Ikeda
K
K
Sato
M
M
Ishii
T
T
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
D016229:Amyloid beta-Peptides; D003176:Complement C3; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor