BETA-AMYLOID PROTEIN ENHANCES MACROPHAGE PRODUCTION OF OXYGEN-FREE RADICALS AND GLUTAMATE

Cells of the monocyte phagocytic system can generate superoxide and gl utamate anions, both of which are neurotoxic at high levels. We used r at peritoneal macrophages as a model system to test the effects of var ious stimulants on the production of these molecules. Glutamate produc tion by such cells was enhanced, in a concentration-dependent manner, by treatment with serum-opsonized zymosan (OZ), lipopolysaccharide (LP S), phorbol myristate acetate (PMA), and beta-amyloid peptide A beta ( 1-40); but not by treatment with the reverse A beta (40-1) or the A be ta (25-35) subfragment. Superoxide anion production by the cells was s timulated by OZ, PMA, A beta (1-40), and A beta (25-35). Moreover, A b eta and its subfragment, when used as priming agents, also enhanced th e stimulatory effect of PMA. However, they did not act as priming agen ts for OZ, suggesting a competition for receptors or intracellular sig naling pathways linked to those receptors. Inflammatory mediators, inc luding A beta, could place glutamate-sensitive neurons at risk by enha ncing glutamate and oxygen free radical production by monocyte-derived cells. Such mechanisms could contribute to the pathogenesis of neurod egenerative disorders, including Alzheimer's disease. (C) 1997 Wiley-L iss, Inc.