HOST PLASMA LOW-DENSITY-LIPOPROTEIN PARTICLES AS AN ESSENTIAL SOURCE OF LIPIDS FOR THE BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI

In contrast to mammalian cells, bloodstream forms of Trypanosoma bruce i show no activity for fatty acid and sterol synthesis and critically depend on plasma low density lipoprotein (LDL) particles for their rap id growth, We report here that these parasites acquire such lipids by receptor-mediated endocytosis of LDL, subsequent lysosomal degradation of apoprotein B-LDL, and utilization of these lipids, Uptake of LDL-a ssociated [H-3]sphingomyelin and of LDL-associated [H-3]cholesteryl ol eate paralleled each other, and that of I-125-apoprotein B-LDL showed saturation and could be inhibited by unlabeled LDL or by anti-LDL rece ptor antibodies. Metabolism of lipids carried by LDL was abolished by chloroquine and by the thiol protease inhibitor, leupeptin, Sphingomye lin was cleaved by an acid sphingomyelinase to yield ceramide, which w as itself split up into sphingosine and fatty acids. The latter were f urther incorporated into phosphatidylcholine, triacylglycerols, or cho lesteryl esters, Similarly, cholesteryl oleate was hydrolyzed by an ac id lipase to yield free cholesterol, which was reesterified with fatty acids, presumably in the cytosol. Like free cholesterol, LDL provided substrate for cholesterol esterification. In the culture-adapted proc yclic form of T. brucei, which is capable of sterol synthesis, exogeno us LDL-cholesterol rather than endogenously synthesized sterol was uti lized for sterol esterification. Interference with exogenous supply of lipids via receptor-mediated endocytosis of LDL should be explored to fight against trypanosomiasis.