Receptor-mediated endocytosis of immunoglobulin-coated colloidal gold particles in cultured mouse peritoneal macrophages. Chloroquine and monensin inhibit transfer of the ligand from endocytic vesicles to lysosomes.
Earlier studies have shown that immunoglobulin G (IgG)-coated colloidal gold particles bind to specific receptors on the macrophage surface and accumulate in coated pits. They are then internalized via endocytic vesicles and transferred to lysosomes. During this process the plasma membrane is depleted of binding sites for IgG, suggesting that both the receptor and the ligand end up in lysosomes. Here, we have examined the effects of the weak base chloroquine and the Na+-H+ ionophore monensin on endocytosis and intracellular transport of IgG-coated colloidal gold particles in cultured macrophages. The results indicate that chloroquine and monensin do not arrest uptake of IgG-coated particles bound to the cell surface. On the other hand, the drugs strongly inhibit transfer of the particles from endocytic vesicles to lysosomes, the latter marked by prior pulse-chase labeling of the cells with horseradish peroxidase. Since the main effect shared by chloroquine and monensin is to raise pH in acid compartments such as endocytic vesicles and lysosomes, the findings suggest that the transfer of IgG-coated particles into the lysosomes is a pH-dependent process. It remains to be shown whether it is the membrane fusion as such that is controlled by pH or, more specifically, the transfer of receptor-bound ligands into the lysosomes.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D005663:Furans / Q000494:pharmacology*; D006046:Gold; D006735:Horseradish Peroxidase; D007074:Immunoglobulin G / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008985:Monensin / Q000494:pharmacology*; D010529:Peritoneal Cavity / Q000166:cytology; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000502:physiology*
D005663:Furans; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D006046:Gold; D002738:Chloroquine; D008985:Monensin; D006735:Horseradish Peroxidase