Amyloid beta protein primes cultured rat microglial cells for an enhanced phorbol 12-myristate 13-acetate-induced respiratory burst activity.
Activated microglia, often associated with neuritic amyloid plaques in the Alzheimer's disease brain, are likely to contribute to the progression of the disease process, e.g., by releasing neurotoxic reactive oxygen and/or nitrogen intermediates. In the present study, whether the amyloid beta peptide (A beta), the principal constituent of amyloid plaques, can stimulate microglial respiratory burst activity and/or microglial production of nitric oxide was examined. Using neonatal rat microglial cultures as a model, it was found that neither the spontaneous release of nitric oxide nor the lipopolysaccharide-induced production of nitric oxide was altered in cultures previously incubated with synthetic A beta (1-40) for 24 h. In addition, no direct stimulatory effect of A beta (1-40) on the respiratory burst activity was observed. Nevertheless, concomitant with an increase in the number of responsive cells, a profound priming of the phorbol 12-myristate 13-acetate-evoked production of superoxide anion was observed in A beta (1-40)-treated cultures. Thus, both the maximal rate and the total phorbol 12-myristate 13-acetate-induced production of superoxide appeared to be statistically significantly higher as compared with untreated cultures. It is concluded that, as far as activation of the microglial respiratory burst is concerned, A beta(1-40) may merely act as a priming rather than a triggering stimulus.
Van Muiswinkel
F L
FL
Department of Psychiatry, Faculty of Medicine, Research Institute Neurosciences Vrije Universiteit, Amsterdam, The Netherlands.
Veerhuis
R
R
Eikelenboom
P
P
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D008070:Lipopolysaccharides; D009573:Nitrites; D013481:Superoxides; D009569:Nitric Oxide; D013755:Tetradecanoylphorbol Acetate