Ammonia inhibits phagosome-lysosome fusion in macrophages

Abstract

When foreign bodies, including many microorganisms, are ingested by cultured macrophages, they become enclosed in phagosomes, with which lysosomes usually fuse and then discharge their enzymes and other contents into the resulting phagolysosomes. Such fusion is, however, diminished or absent after the phagocytosis of some pathogens, notably Mycobacterium tuberculosis and Toxoplasma gondii. Assuming that the nonfusion is due to active inhibition by the intrapoagosomal microbe, identification of an inhibitor should clarify the lysosomal control mechanism. It has been suggested that strongly acidic sulphatides present in virulent tuberculosis, which, like other substances with polyanionic structural features, can themselves block phagosome-lysosome fusion (P-LF), may contribute to the negative lysosome response to ingested tubercle bacilli. We report here another possibility, based on inhibition of fusion of yeast-containing phagosomes by filtrates from cultures of tubercle bacilli on traditional-type defined media; we show that the ammonia content of such filtrates is sufficient to account for their effect. This inhibition of fusion seems to be an hitherto unrecognized intracellular consequence of added ammonia, in striking contrast to the enhancement produced by some lipophilic amines.