Effects of oxygen-centred free radicals on low-density lipoprotein structure and metabolism

Abstract

The present study shows that trypanosomes are able to obtain cholesterol by taking up and degrading human LDL, a process which increases intracellular cholesterol esterification. Presumably other lipoprotein particles which show similar binding to that of LDL, such as E-HDL, may also be taken up by trypanosomes and their cholesterol utilized. In some host species LDL may be present only in low concentrations or even absent (Chapman, 1980) and such alternative lipoproteins may be the major source of cholesterol for the parasite. However, it is clear from the present results that human A-HDL is unlikely to serve as a significant source of cholesterol for the parasite. In man, T . hrucei hrucei is not normally infective and the parasite is lysed on exposure to human plasma. Rifkin (1978) has identified the trypanocidal factor present in human plasma as highdensity lipoprotein, presumably the major fraction, A-HDL. The mode of action of A-HDL is unknown, but the suggestion that it is taken up by trypanosomes, causing massive accumulation of cholesteryl esters and release of autolytic enzymes (Ormerod, 1985), may be discarded. Instead, since A-HDL is saturably bound by T . hrucei hrucei (Gillett & Owen, 1987), is poorly degraded and inhibits, rather than stimulates, intracellular cholesterol esterification it is more probable that the lethal action of this lipoprotein occurs directly at the trypanosome surface.