Effect of ammonia on endocytosis and cytokine production by immortalized human microglia and astroglia cells

Abstract

Ammonium acetate decreased in a concentration-dependent manner the phagocytic uptake of mannosylated latex microspheres and of yeast by immortalized human microglia (CHME-5) and astroglioma (GL-15) cells. In both cell lines ammonium acetate affected also the secretion of certain cytokines. The most conspicuous effects were the following: in both cell lines ammonium acetate enhanced greatly the secretion of tumor necrosis factor-α in the absence of any other stimulus. In the human microglia cells ammonia decreased the constitutive secretion of interleukin-6, but it enhanced the stimulated (interleukin-1α, tumor necrosis factor-α, γ-interferon and γ-interferon + tumor necrosis factor-α) secretion of interleukin-8. In the astroglioma cell line, the stimulated release of tumor necrosis factor-α, interleukin-6 and interleukin-8 was diminished by ammonium acetate. The magnitude of the ammonia-effect depended on the stimulating agent (lipopolysaccharide, interleukin-1α, tumor necrosis factor-α, γ-interferon). The results are discussed with regard to their potential importance in the pathogenesis of human diseases with elevated blood and brain ammonia concentrations.