ABSTRACT
The macrophage cell-line J774.E1 and Leishmania m. mexicana infection was used to investigate the uptake of liposomes, which differed in their bulk phospholipid: ester- or ether-analogue of phosphatydilcholine (PC). The receptor-mediated uptake of both species of liposomes, containing native or acetylated LDL as ligands was also evaluated. Uninfected and infected J774.E1 cell-line accumulated more ester- and ether-liposomes alone than mixed type (50:50, ester/ether). The utilization was significantly enhanced when both types of liposomes contained native LDL. The highest uptake was recorded for liposomes bearing acetylated LDL by infected J774.E1 cells. Accumulation of ester- and ether-liposomes with the same ligand was not markedly affected by different chemical nature of PC. Finally, ether-liposomes alone possessed certain activity against Leishmania m. mexicana amastigotes. The results presented here demonstrated the usefulness of ether-liposomes with specific ligands in site-specific delivery of antileishmanial compounds in vitro.
Subject(s)
Leishmania mexicana/physiology , Liposomes/metabolism , Macrophages/metabolism , Macrophages/parasitology , Phagocytosis/physiology , 1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives , 1,2-Dipalmitoylphosphatidylcholine/analysis , Acetylation , Animals , Apolipoproteins B/analysis , Cell Line , Kinetics , Leishmania mexicana/drug effects , Ligands , Lipoproteins, LDL/analysis , Lipoproteins, LDL/metabolism , Liposomes/chemistry , Macrophages, Peritoneal/parasitology , Organophosphates/analysis , Phospholipid Ethers/analysisABSTRACT
Three acidic unsaponifiable lipid fractions were isolated by chromatographic methods from sandfly vector stages (promastigotes) of a protozoan parasite of man, Leishmania mexicana mexicana, cultured in vitro. Fast atom bombardment mass spectrometry, fast atom bombardment collision induced tandem mass spectrometry and metabolic labeling were used to characterize these lipids as di-O-alkylphosphatidyl-inositols, lyso-1-O-alkylphosphatidylinositols and inositol phosphosphingolipids. Molecular species of the dialkyl forms, new to natural product biochemistry, had a 20:0 substituent and either 17:1 or 18:1. The monoalkyl forms had either 17:0 or 18:0. The predominant ceramide had the 16:1 base and the lesser component the 16:0 base. In both, the N-acyl group was 18:0.