BETA-AMYLOID PEPTIDE INDUCES TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE PRODUCTION IN MURINE MACROPHAGE CULTURES

We investigated the effect of beta-amyloid peptide (beta A) on the act ivation of the murine-derived monocyte/macrophage J774 cell-line. beta A induced tumor necrotic factor-alpha (TNF alpha) in these cells in a dose-dependent manner. Incubation of cells with beta A slightly incre ased nitric oxide (NO) production, an effect that was significantly en hanced by the addition of interferon-gamma (IFN gamma). Substitution o f beta A4 with TFN alpha. and incubation of the cultures with IFN gamm a resulted in significant NO production, although this was lower than that obtained in the presence of the peptide. Incubation of cultures w ith a monoclonal antibody (mAb) against TNF alpha abrogated NO product ion. Our results suggest that beta A4-induced TNF alpha production is a crucial event in the activation of peripheral macrophages.