title: Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.
abstract: To investigate whether the lysosomes of Trypanosoma brucei are capable of uptake of macromolecules after internalization by the cell, we used Triton WR-1339, a non-digestible macromolecular compound, which is known to cause a marked decrease in the density of hepatic lysosomes due to massive intralysosomal storage. Intraperitoneal administration of 0.4 g/kg Triton WR-1339 to rats infected with T. brucei led to the development of a large vacuole in the trypanosomes between nucleus and kinetoplast within 22 h. Higher doses (2 g/kg) led to the disappearance of the trypanosomes from the blood and resulted in permanent cures (greater than 100 days). Lysosomes isolated from the trypanosomes of animals treated with a sub-curative dose showed a decrease in equilibrium density of 0.03 g/cm3 in sucrose gradients. These lysosomes were partly damaged as evidenced by a reduction in latency and an increase in the non-sedimentable part of lysosomal enzymes. We conclude that acid proteinase and alpha-mannosidase-containing organelles of T. brucei take up exogenous macromolecules and must therefore be considered as true lysosomes and that Triton WR-1339 acts in T. brucei as a true lysosomotropic drug. Its trypanocidal action probably results from an interference with lysosomal function.
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002499:Centrifugation, Density Gradient; D010450:Endopeptidases / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008361:Mannosidases / Q000378:metabolism; D051379:Mice; D011092:Polyethylene Glycols / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D014346:Trypanosoma brucei brucei / Q000378:metabolism* / Q000648:ultrastructure; D014353:Trypanosomiasis, African / Q000188:drug therapy; D043323:alpha-Mannosidase
chemical_list: D011092:Polyethylene Glycols; D008361:Mannosidases; D043323:alpha-Mannosidase; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C016811:tyloxapol