Mechanism of resistance of African trypanosomes to cytotoxic human HDL.
Trypanosoma brucei brucei, the causative agent of ngana in cattle, is non-infectious to humans because of its sensitivity to the cytolytic activity of normal human serum. The toxin in normal human serum is human haptoglobin-related protein (Hpr) which is found either as an apolipoprotein associated with a minor subclass of high-density lipoprotein (HDL), named trypanosome lytic factor (TLF1), or as an unstable, high-molecular-mass protein complex known as TLF2 (refs 5, 9-12). TLF-mediated lysis of T. b. brucei requires binding, internalization and lysosomal targeting. The human sleeping-sickness trypanosome, Trypanosoma brucei rhodesiense is resistant to TLF. Our studies reveal 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-sickness trypanosomes to human serum is decreased internalization of receptor-bound TLF.
Hager
K M
KM
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Schools of Medicine and Dentistry, 35294-0005, USA.
Hajduk
S L
SL
D000818:Animals; D000951:Antigens, Neoplasm; D001798:Blood Proteins / Q000502:physiology; D004705:Endocytosis; D006242:Haptoglobins; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D016833:Trypanosoma brucei rhodesiense / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000502:physiology*
D000951:Antigens, Neoplasm; D001798:Blood Proteins; C058632:HPR protein, human; D006242:Haptoglobins; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; D014168:Transferrin; D014643:Variant Surface Glycoproteins, Trypanosoma