Alzheimer's disease amyloid beta and prion protein amyloidogenic peptides promote macrophage survival, DNA synthesis and enhanced proliferative response to CSF-1 (M-CSF).
Microglial cells, macrophage-lineage cells in the brain, are increased in amyloid-containing plaques in Alzheimer's disease (AD) and in the lesions of prion diseases. Recent studies suggest that microglia have a central role in turnover of amyloid in these diseases. We report here that synthetic amyloid beta (Abeta) 1-42 and prion protein (PrP) 106-126 peptides promote macrophage survival; they also induce macrophage DNA synthesis, particularly in the presence of sub-optimal concentrations of the growth factor, macrophage-colony stimulating factor (M-CSF or CSF-1). These responses are proposed to provide a means to increase brain microglia/macrophage numbers thereby enhancing subsequent inflammatory/immune responses. These fibrillogenic peptides join the list of aggregates having these effects on macrophages, indicating the generality of this type of response.
Hamilton
John A
JA
Arthritis and Inflammation Research Centre, The University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Clinical Sciences Building, Royal Parade, Victoria 3050, Parkville, Australia. jahami@unimelb.edu.au
Whitty
Genevieve
G
White
Anthony R
AR
Jobling
Michael F
MF
Thompson
Andrew
A
Barrow
Colin J
CJ
Cappai
Roberto
R
Beyreuther
Konrad
K
Masters
Colin L
CL
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000494:pharmacology*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011328:Prions; C075222:amyloid beta-protein (1-42); C082632:prion protein (106-126); D016173:Macrophage Colony-Stimulating Factor; D004247:DNA