Involvement of lysosomes in the uptake of macromolecular material by bloodstream forms of Trypanosoma brucei.
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.
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
D011092:Polyethylene Glycols; D008361:Mannosidases; D043323:alpha-Mannosidase; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C016811:tyloxapol