Activation of macrophages by Alzheimer beta amyloid peptide.
Microglia (brain resident macrophages) have been found to be closely associated with beta amyloid containing plaques in brain tissue affected by Alzheimer disease (AD). To investigate whether beta amyloid peptide (beta AP) may activate microglia, the effects of synthetic beta AP (amino acids 1-40) and a subfragment (amino acids 25-35) on rat peritoneal macrophages were assessed using four different assays for activation. These peptides were compared with substance P, which has previously been shown to activate macrophages. Both beta amyloid peptides activated macrophages, as assessed by increased respiratory burst-associated oxygen consumption, by luminol-dependent chemiluminescence, and by aggregation. In addition, beta amyloid peptide (1-40) caused a significant increase in macrophage nitric oxide production, while subfragment (25-35) did not. Substance P caused significant activation as assessed by oxygen consumption and chemiluminescence, but not by aggregation or nitric oxide induction.
Klegeris
A
A
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Walker
D G
DG
McGeer
P L
PL
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D007700:Kinetics; D008163:Luminescent Measurements; D008165:Luminol; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D017628:Microglia / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D008165:Luminol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases