MECHANISM OF RESISTANCE OF AFRICAN TRYPANOSOMES TO CYTOTOXIC HUMAN HDL

Trypanosoma brucei brucei the causative agent of ngana in cattle, is n on-infectious to humans because of its sensitivity to the cytolytic ac tivity of normal human serum(1). The toxin in normal human serum is hu man haptoglobin-related protein (Hpr)(2-5) which is found either as an apolipoprotein associated with a minor subclass of high-density lipop rotein (HDL), named trypanosome lytic factor (TLF1)(6-8), or as an uns table, high-molecular-mass protein complex known as TLF2 (refs 5, 9-12 ). TLF-mediated lysis of T. b. brucei requires binding, internalizatio n and lysosomal targeting(13). The human sleeping-sickness trypanosome , Trypanosoma brucei rhodesiense is resistant to TLF. Our studies reve al that resistant trypanosomes fail to endocytose TLF yet continue to bind TLF through cell-surface receptors. On the basis of these results , we conclude that one mechanism of resistance of human sleeping-sickn ess trypanosomes to human serum is decreased internalization of recept or-bound TLF.