Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum

Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4118-23. doi: 10.1073/pnas.0609902104. Epub 2007 Feb 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / blood
  • Antigens, Neoplasm / physiology*
  • Apolipoprotein L1
  • Apolipoproteins / blood
  • Apolipoproteins / physiology*
  • Blood Proteins / physiology*
  • Blotting, Western
  • Chromatography, Affinity
  • Haptoglobins / physiology*
  • Humans
  • Immune System
  • Kinetics
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / physiology*
  • Mice
  • Recombinant Proteins / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma brucei brucei / metabolism
  • Trypanosomiasis, African / drug therapy


  • APOL1 protein, human
  • Antigens, Neoplasm
  • Apolipoprotein L1
  • Apolipoproteins
  • Blood Proteins
  • HPR protein, human
  • Haptoglobins
  • Lipoproteins, HDL
  • Recombinant Proteins
  • Trypanocidal Agents