The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20071463
The Journal of Experimental Medicine, Vol. 205, No. 8, 1721-1728
The Rockefeller University Press, 0022-1007 $30.00
© Molina-Portela et al.
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BRIEF DEFINITIVE REPORT

Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model

Maria Pilar Molina-Portela, Marie Samanovic, and Jayne Raper

Department of Medical Parasitology, New York University Langone Medical Center/School of Medicine, New York, NY 10010

CORRESPONDENCE Jayne Raper: jr57{at}nyu.edu

Humans express a unique subset of high-density lipoproteins (HDLs) called trypanosome lytic factors (TLFs) that kill many Trypanosoma parasite species. The proteins apolipoprotein (apo) A-I, apoL-I, and haptoglobin-related protein, which are involved in TLF structure and function, were expressed through the introduction of transgenes in mice to explore their physiological roles in vivo. Transgenic expression of human apolipoprotein L-I alone conferred trypanolytic activity in vivo. Coexpression of human apolipoprotein A-I and haptoglobin-related protein (Hpr) had an effect on the integration of apolipoprotein L-I into HDL, and both proteins were required to increase the specific activity of TLF, which was measurable in vitro. Unexpectedly, truncated apolipoprotein L-I devoid of the serum resistance gene interacting domain, which was previously shown to kill human infective trypanosomes, was not trypanolytic in transgenic mice despite being coexpressed with human apolipoprotein A-I and Hpr and incorporated into HDLs. We conclude that all three human apolipoproteins act cooperatively to achieve maximal killing capacity and that truncated apolipoprotein L-I does not function in transgenic animals.


© 2008 Molina-Portela et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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