Effect of ammonia on endocytosis, cytokine production and lysosomal enzyme activity of a microglial cell line.
Ammonia is a natural lysosomotropic compound. Concentrations of ammonium acetate > 2 mM impaired the phagocytic activity of BV-2 cells, an immortalized microglial cell line, as was determined by the uptake of fluorescent latex microspheres of different sizes. In contrast, an increase in the uptake of fluorescent dextran was observed with the elevation in ammonium acetate concentrations. This indicates that ammonia affects phagocytotic and pinocytotic activities of BV-2 cells differently. Interferon-gamma- and polyinosinic-polycytidylic acid-stimulated secretion of IL1 alpha as well as LPS-stimulated secretion of IL6 decreased with an elevation in ammonium acetate concentrations. The constitutive secretion of IL1 alpha was not significantly affected by ammonium acetate. However, an increase in LPS-stimulated IL1 alpha secretion was observed at 10 mM and 20 mM ammonium acetate. High concentrations of 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 respect to pathogenetic mechanisms of dementia of the Alzheimer type.
Atanassov
C L
CL
UPR 9021, Immunochimie des Peptides et des Virus, Institut de Biologie moléculaire et cellulaire du CNRS, Strasbourg, France.
Muller
C D
CD
Sarhan
S
S
Knödgen
B
B
Rebel
G
G
Seiler
N
N
D000085:Acetates / Q000494:pharmacology; D000135:Acid Phosphatase / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D004705:Endocytosis / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001617:beta-Glucosidase / Q000378:metabolism
D000085:Acetates; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000641:Ammonia; D000135:Acid Phosphatase; D001617:beta-Glucosidase; D002402:Cathepsin D; C018824:ammonium acetate