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 progre ssion of the disease process, e.g., by releasing neurotoxic reactive o xygen and/or nitrogen intermediates. In the present study, whether the amyloid beta peptide (A beta), the principal constituent of amyloid p laques, can stimulate microglial respiratory burst activity and/or mic roglial production of nitric oxide was examined. Using neonatal rat mi croglial cultures as a model, it was found that neither the spontaneou s release of nitric oxide nor the lipopolysaccharide-induced productio n of nitric oxide was altered in cultures previously incubated with sy nthetic A beta(1-40) for 24 h. In addition, no direct stimulatory effe ct of A beta(1-40) on the respiratory burst activity was observed. Nev ertheless, concomitant with an increase in the number of responsive ce lls, a profound priming of the phorbol 12-myristate 13-acetate-evoked production of superoxide anion was observed in A beta(1-40)-treated cu ltures. Thus, both the maximal rate and the total phorbol 12-myristate 13-acetate-induced production of superoxide appeared to be statistica lly significantly higher as compared with untreated cultures. It is co ncluded 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.