Lung macrophage defense responses during suramin-induced lysosomal dysfunction

Lysosomes form an integral part of the degradative mechanisms of the phagocytic cells. Mice were injected with suramin, a lysosomotrophic drug, to investigate the effects of lysosomal pathology on the cell biology and in situ bactericidal activity of the pulmonary macrophage. Treatment with suramin resulted in marked alterations in the cell biology of the macrophage: (i) increased vacuolization and protein content, (ii) suppressed intracellular phagosome-lysosome fusion, (iii) decreased activity of the lysosomal enzymes β-glucuronidase and N-acetyl-glucosaminidase, and (iv) enhanced exocytosis of acid phosphatase during phagocytosis. Addition of suramin, in vitro, to cell lysates resulted in a reduction in the catalytic activities of acid phosphatase, β-glucuronidase, and N-acetyl-glucosaminidase; thereby suggesting that selective interaction, in vivo, between suramin and lysosomes containing β-glucuronidase and N-acetyl-glucosaminidase may have occurred. Plasma membrane 5′-nucleotide phosphodiesterase activity was increased in macrophages recovered from suramin-treated animals. Although the "resting-state" reduction of nitroblue tetrazolium (NBT) was lower in these macrophages, cells stimulated by a phagocytic challenge demonstrated normal increases in NBT reduction. Phagocytosis, in vitro, and pulmonary bactericidal activity were not altered. These data demonstrate that suramin altered numerous aspects of the phagocyte's lysosomal system. Despite these changes in the cell biology of the pulmonary macrophage, the cell's defense functions were not reduced.