Receptor-mediated entry of peroxidases into the parasitophorous vacuoles of macrophages infected with Leishmania Mexicana amazonensis.
Leishmania amastigotes, obligatory parasites of macrophages, lodge and multiply within long-lived phagolysosomelike "parasitophorous vacuoles" (PV). The glycoprotein horseradish peroxidase (HRP) was shown, by light and electron microscopic cytochemistry, to enter the PVs of rat in vitro-derived bone marrow macrophages infected with Leishmania mexicana amazonensis. Uptake was obtained both in preinfected macrophages incubated with HRP and in macrophages pulsed with HRP, infected, and further incubated in ligand-free medium. Peroxidase positive and negative PVs could coexist in the same macrophages. Infected macrophages commonly displayed fewer labeled secondary lysosomes than noninfected cells. Lactoperoxidase (LP) was also shown, by light microscopy, to enter the PVs of rat macrophages. Uptake of HRP and of LP was blocked by mannan, supporting the mannose receptor mediated recognition of these ligands. Transfer of HRP to PVs was much less efficient in resident mouse peritoneal macrophages, even at 50 X higher ligand concentrations. Such macrophages expressed negligible mannose receptor function. The efficient mannan-inhibitable uptake of HRP by rat marrow macrophages was confirmed biochemically. Bulk HRP uptake in infected and noninfected cultures was found to be similar. Peroxidases should be useful in further studies of endocytosis by Leishmania-infected macrophages and in the development of lysosomotropic macrophage-targeted drug carriers.
D000818:Animals; D001854:Bone Marrow Cells; D005260:Female; D006735:Horseradish Peroxidase / Q000378:metabolism; D007784:Lactoperoxidase / Q000378:metabolism; D007891:Leishmania / Q000502:physiology*; D008264:Macrophages / Q000469:parasitology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000494:pharmacology*; D014617:Vacuoles / Q000469:parasitology
D011955:Receptors, Drug; D006735:Horseradish Peroxidase; D007784:Lactoperoxidase