Monensin and chloroquine inhibit transfer to lysosomes of endocytosed macromolecules in cultured mouse peritoneal macrophages.

摘要: The effects of the Na+/H+ ionophore monensin and weak base chloroquine on lysosomal uptake endocytosed macromolecules were studied in cultured mouse peritoneal macrophages using horseradish peroxidase (HRP) ferritin as exogenous tracers. lysosomes first loaded with HRP a pulse-chase protocol. cells then exposed to for 30 120 min, either control medium or containing 3 microM 50 chloroquine. Semiquantitative electron microscopic analyses indicated that into HRP-labeled was inhibited drug-treated cells, tracer particles accumulated endosomes. At same time volume density endosomes increased, fourfold by threefold chloroquine; latter drug there also an increase lysosome density. Further, both drugs decreased rate endocytosis measured biochemically, but not proportion reduction uptake. After withdrawal drugs, cell morphology returned normal transfer from resumed. recovery more rapid complete monensin-treated than chloroquine-treated cells. On basis these findings earlier investigations demonstrating raise pH acid compartments, it is suggested soluble only membrane-bound modulated organelles.