Receptor-mediated entry of beta-glucuronidase into the parasitophorous vacuoles of macrophages infected with Leishmania mexicana amazonensis.

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Abstract
125I-labeled rat preputial gland .beta.-glucuronidase was shown by light microscopic and EM radioautography to accumulate within the parasitophorous vacuoles of in vitro derived [mouse] bone marrow macrophages infected with L. m. amazonensis. .beta.-Glucuronidase uptake was mediated by the mannose receptor, since the penetration of the ligand was inhibited by mannan. Uptake was detected as soon as 4 h after incubation of infected cells with the ligand, and increased at 24 and 48 h. The label persisted in the vacuoles for at least 24 h after a 24-h pulse with the ligand, a finding compatible with the relatively long half-life of labeled .beta.-glucuronidase in normal macrophages. Parasitophorous vacuoles were also labeled in macrophages exposed to the ligand only before infection, indicating that secondary lysosomes containing the ligand fused with the parasitophorous vacuoles. Another mannosylated ligand, mannose-BSA [bovine serum albumin], which, in contrast to .beta.-glucuronidase, is rapidly degraded in macrophage lysosomes, did not detectably accumulate in the vacuoles. The results support and extend information previously obtained with electron opaque tracers that emphasizes the phagolysosomal nature of Leishmania parasitophorous vacuoles. Appropriate mannosylated molecules may be used as carriers for targeting or leishmanicidal drugs to the parasitophorous vacuoles of infected macrophages.

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