EFFECT OF AMMONIA ON ENDOCYTOSIS AND CYTOKINE PRODUCTION BY IMMORTALIZED HUMAN MICROGLIA AND ASTROGLIA CELLS

Ammonium acetate decreased in a concentration-dependent manner the pha gocytic uptake of mannosylated latex microspheres and of yeast by immo rtalized human microglia (CHME-5) and astroglioma (GL-15) cells. In bo th cell lines ammonium acetate affected also the secretion of certain cytokines. The most conspicuous effects were the following : in both c ell lines ammonium acetate enhanced greatly the secretion of tumor nec rosis factor-alpha in the absence of any other stimulus. In the human microglia cells ammonia decreased the constitutive secretion of interl eukin-6, but it enhanced the stimulated (interleukin-1 alpha, tumor ne crosis factor-alpha, gamma-interferon and gamma-interferon + tumor nec rosis factor-alpha) secretion of interleukin-8. In the astroglioma cel l line, the stimulated release of tumor necrosis factor-alpha, interle ukin-6 and interleukin-8 was diminished by ammonium acetate. The magni tude of the ammonia-effect depended on the stimulating agent (lipopoly saccharide, interleukin-1 alpha, tumor necrosis factor-alpha, gamma-in terferon). The results are discussed with regard to their potential im portance in the pathogenesis of human diseases with elevated blood and brain ammonia concentrations.