Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum
- 6 March 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (10), 4118-4123
- https://doi.org/10.1073/pnas.0609902104
Abstract
Apolipoprotein L-I (apoL-I) is a human high-density lipoprotein (HDL) component able to kill Trypanosoma brucei brucei by forming anion-selective pores in the lysosomal membrane of the parasite. Another HDL component, haptoglobin-related protein (Hpr), has been suggested as an additional toxin required for full trypanolytic activity of normal human serum. We recently reported the case of a human lacking apoL-I (apoL-I(-/-)HS) as the result of frameshift mutations in both apoL-I alleles. Here, we show that this serum, devoid of any trypanolytic activity, exhibits normal concentrations of HDL-bound Hpr. Conversely, the serum of individuals with normal HDL-bound apoL-I but who lack Hpr and haptoglobin [Hp(r)(-/-)HS] as the result of gene deletion (anhaptoglobinemia) exhibited phenotypically normal but delayed trypanolytic activity. The trypanolytic properties of Hp(r)(-/-)HS were mimicked by free recombinant apoL-I, whereas recombinant Hpr did not affect trypanosomes. The lysis delay observed with either Hp(r)(-/-)HS or recombinant apoL-I could entirely be attributed to a defect in the uptake of the lytic components. Thus, apoL-I is responsible for the trypanolytic activity of normal human serum, whereas Hpr allows fast uptake of the carrier HDL particles, presumably through their binding to an Hp/Hpr surface receptor of the parasite.Keywords
This publication has 35 references indexed in Scilit:
- The Genome of the African Trypanosome Trypanosoma bruceiScience, 2005
- Apolipoprotein L-I is the trypanosome lytic factor of human serumNature, 2003
- Evidence for a Trypanosoma brucei Lipoprotein Scavenger ReceptorPublished by Elsevier BV ,2003
- CD163: a signal receptor scavenging haptoglobin–hemoglobin complexes from plasmaThe International Journal of Biochemistry & Cell Biology, 2002
- The Haptoglobin-Gene Deletion Responsible for AnhaptoglobinemiaAmerican Journal of Human Genetics, 1998
- Mechanism of resistance of African trypanosomes to cytotoxic human HDLNature, 1997
- The main lytic factor of Trypanosoma brucei brucei in normal human serum is not high density lipoprotein.The Journal of Experimental Medicine, 1996
- Importance of acidic intracellular compartments in the lysis of Trypanosoma brucei brucei by normal human serumTransactions of the Royal Society of Tropical Medicine and Hygiene, 1994
- Identification of Proteins Associated with Apolipoprotein A-I-Containing Lipoproteins Purified by Selected-Affinity ImmunosorptionBiochemistry, 1994
- Trypanosoma brucei brucei: differences in the trypanocidal activity of human plasma and its relationship to the level of high density lipoproteinsTransactions of the Royal Society of Tropical Medicine and Hygiene, 1991