EFFECT OF AMMONIA ON ENDOCYTOSIS, CYTOKINE PRODUCTION AND LYSOSOMAL-ENZYME ACTIVITY OF A MICROGLIAL CELL-LINE

Ammonia is a natural lysosomotropic compound. Concentrations of ammoni um acetate > 2 mM impaired the phagocytic activity of BV-2 cells, an i mmortalized microglial cell line, as was determined by the uptake of f luorescent latex microspheres of different sizes. In contrast, an incr ease in the uptake of fluorescent dextran was observed with the elevat ion in ammonium acetate concentrations. This indicates that ammonia af fects phagocytotic and pinocytotic activities of BV-2 cells differentl y. Interferon-gamma- and polyinosinic-polycytidylic acid-stimulated se cretion of IL1 alpha as well as LPS-stimulated secretion of IL6 decrea sed with an elevation in ammonium acetate concentrations. The constitu tive secretion of IL1 alpha was not significantly affected by ammonium acetate. However, an increase in LPS-stimulated IL1 alpha secretion w as observed at 10 mM and 20 mM ammonium acetate. High concentrations o f ammonia affected the activity of lysosomal enzymes of the BV-2 cells . Acid phosphatase and alpha-glucosidase activities increased with the increase in ammonium acetate up to 20 mM. The activity of cathepsin D was increased at 5 mM, but decreased at higher ammonia concentrations . The effects of ammonia on microglial functions are discussed with re spect to pathogenetic mechanisms of dementia of the Alzheimer type.