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J Biol Chem. 2005 Sep 23;280(38):32578-85. Epub 2005 Jul 26.

Human high density lipoproteins are platforms for the assembly of multi-component innate immune complexes.

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1
Josephine Bay Paul Center, Global Infectious Disease Program, Marine Biological Laboratory, Woods Hole, Massachussetts 02543, USA.

Abstract

Human innate immunity to non-pathogenic species of African trypanosomes is provided by human high density lipoprotein (HDL) particles. Here we show that native human HDLs containing haptoglobin-related protein (Hpr), apolipoprotein L-I (apoL-I) and apolipoprotein A-I (apoA-I) are the principle antimicrobial molecules providing protection from trypanosome infection. Other HDL subclasses containing either apoA-I and apoL-I or apoA-I and Hpr have reduced trypanolytic activity, whereas HDL subclasses lacking apoL-I and Hpr are non-toxic to trypanosomes. Highly purified, lipid-free Hpr and apoL-I were both toxic to Trypanosoma brucei brucei but with specific activities at least 500-fold less than those of native HDLs, suggesting that association of these apolipoproteins within the HDL particle was necessary for optimal cytotoxicity. These studies show that HDLs can serve as platforms for the assembly of multiple synergistic proteins and that these assemblies may play a critical role in the evolution of primate-specific innate immunity to trypanosome infection.

PMID:
16046400
DOI:
10.1074/jbc.M503510200
[Indexed for MEDLINE]
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