Publication Date:
2022-05-25
Description:
Author Posting. © American Society for Biochemistry and Molecular Biology, 2005. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 280 (2005): 32578-3258, doi:10.1074/jbc.M503510200.
Description:
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.
Description:
These studies were supported by National Institutes of Health Grants AI39033 and
AI054496 and a grant from the Ellison Medical Foundation. Mass spectrometry was
carried out at the University of Alabama at Birmingham Mass Spectrometry Shared
Facility and was supported in part by NCI, National Institutes of Health Core Research
Support Grant P30 CA 1314 to the University of Alabama at Birmingham Comprehensive
Cancer Center.
Repository Name:
Woods Hole Open Access Server
Type:
Article
Format:
application/pdf
Permalink