| Title | Mechanism of resistance of African trypanosomes to cytotoxic human HDL. | | Author(s) | Hager KM, Hajduk SL | | Institution | Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Schools of Medicine and Dentistry, 35294-0005, USA. | | Source | Nature 1997 Feb 27; 385(6619):823-6. | | MeSH | Animals
Antigens, Neoplasm
Blood Proteins
Endocytosis
Haptoglobins
Humans
Lipoproteins, HDL
Mice
Receptors, Cell Surface
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Transferrin
Trypanosoma brucei brucei
Trypanosoma brucei rhodesiense
Variant Surface Glycoproteins, Trypanosoma
| | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 9039915 |
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