HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hajduk, S. L. Articles by Esko, J. D. Search for Related Content PubMed PubMed Citation Articles by Hajduk, S. L. Articles by Esko, J. D. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 264, Issue 9, 5210-5217, Mar, 1989

Lysis of Trypanosoma brucei by a toxic subspecies of human high density lipoprotein

SL Hajduk, DR Moore, J Vasudevacharya, H Siqueira, AF Torri, EM Tytler and JD Esko
Department of Biochemistry, School of Medicine, University of Alabama, Birmingham 35294.

Trypanosoma brucei brucei is an important pathogen of domestic cattle in sub-Saharan Africa and is closely related to the human sleeping sickness parasites, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. However, T. b. brucei is non-infectious to humans. The restriction of the host range of T. b. brucei results from the sensitivity of the parasite to lysis by toxic human high density lipoproteins (HDL) (Rifkin, M. R. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 3450-3454). We show in this report that trypanosome lytic activity is not a universal feature of all human HDL particles but rather that it is associated with a minor subclass of HDL. We have purified the lytic activity about 8,000-fold and have identified and characterized the subspecies of HDL responsible for trypanosome lysis. This class of HDL has a relative molecular weight of 490,000, a buoyant density of 1.21-1.24 g/ml, and a particle diameter of 150-210 A. It contains apolipoproteins AI, AII, CI, CII, and CIII, and monoclonal antibodies against apo-AI and apo-AII inhibit trypanocidal activity. In addition to these common apolipoproteins, the particles also contain at least three unique proteins, as measured by sodium dodecyl sulfate- polyacrylamide gel electrophoresis under nonreducing conditions. Treatment of the particles with dithiothreitol resulted in the disappearance of two of the proteins and abolished trypanocidal activity. Two-dimensional gel electrophoresis showed that these proteins were a disulfide-linked trimer of 45,000, 36,000, and 13,500- Da polypeptides and dimers of the 36,000- and 13,500-Da polypeptides or of 65,000- and 8,500-Da polypeptides. Studies on the lysis of T. b. brucei by the purified particle suggest that the lytic pathway may involve the uptake of the trypanocidal subspecies of HDL by endocytosis.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. Vanhollebeke, M. J. Nielsen, Y. Watanabe, P. Truc, L. Vanhamme, K. Nakajima, S. K. Moestrup, and E. Pays Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum PNAS, March 6, 2007; 104(10): 4118 - 4123. [Abstract] [Full Text] [PDF]

				M. J. Nielsen, S. V. Petersen, C. Jacobsen, S. Thirup, J. J. Enghild, J. H. Graversen, and S. K. Moestrup A Unique Loop Extension in the Serine Protease Domain of Haptoglobin Is Essential for CD163 Recognition of the Haptoglobin-Hemoglobin Complex J. Biol. Chem., January 12, 2007; 282(2): 1072 - 1079. [Abstract] [Full Text] [PDF]

				M. J. Nielsen, S. V. Petersen, C. Jacobsen, C. Oxvig, D. Rees, H. J. Moller, and S. K. Moestrup Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein Blood, October 15, 2006; 108(8): 2846 - 2849. [Abstract] [Full Text] [PDF]

				A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]

				S. D. Faulkner, M. W. Oli, R. Kieft, L. Cotlin, J. Widener, A. Shiflett, M. J. Cipriano, S. E. Pacocha, S. R. Birkeland, S. L. Hajduk, et al. In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei. Eukaryot. Cell, August 1, 2006; 5(8): 1276 - 1286. [Abstract] [Full Text] [PDF]

				M. W. Oli, L. F. Cotlin, A. M. Shiflett, and S. L. Hajduk Serum Resistance-Associated Protein Blocks Lysosomal Targeting of Trypanosome Lytic Factor in Trypanosoma brucei Eukaryot. Cell, January 1, 2006; 5(1): 132 - 139. [Abstract] [Full Text] [PDF]

				A. M. Shiflett, J. R. Bishop, A. Pahwa, and S. L. Hajduk Human High Density Lipoproteins Are Platforms for the Assembly of Multi-component Innate Immune Complexes J. Biol. Chem., September 23, 2005; 280(38): 32578 - 32585. [Abstract] [Full Text] [PDF]

				M. M. A. Whitten, I. F. Tew, B. L. Lee, and N. A. Ratcliffe A Novel Role for an Insect Apolipoprotein (Apolipophorin III) in {beta}-1,3-Glucan Pattern Recognition and Cellular Encapsulation Reactions J. Immunol., February 15, 2004; 172(4): 2177 - 2185. [Abstract] [Full Text] [PDF]

				J. Raper, R. Fung, J. Ghiso, V. Nussenzweig, and S. Tomlinson Characterization of a Novel Trypanosome Lytic Factor from Human Serum Infect. Immun., April 1, 1999; 67(4): 1910 - 1916. [Abstract] [Full Text] [PDF]

				C. Grunfeld, M. Marshall, J. K. Shigenaga, A. H. Moser, P. Tobias, and K. R. Feingold Lipoproteins inhibit macrophage activation by lipoteichoic acid J. Lipid Res., February 1, 1999; 40(2): 245 - 252. [Abstract] [Full Text]

				G. Hide History of Sleeping Sickness in East Africa Clin. Microbiol. Rev., January 1, 1999; 12(1): 112 - 125. [Abstract] [Full Text] [PDF]

				B. Garner, A. R. Waldeck, P. K. Witting, K.-A. Rye, and R. Stocker Oxidation of High Density Lipoproteins. II. EVIDENCE FOR DIRECT REDUCTION OF LIPID HYDROPEROXIDES BY METHIONINE RESIDUES OF APOLIPOPROTEINS AI AND AII J. Biol. Chem., March 13, 1998; 273(11): 6088 - 6095. [Abstract] [Full Text] [PDF]

				C. T. Park and S. D. Wright Plasma Lipopolysaccharide-binding Protein Is Found Associated with a Particle Containing Apolipoprotein A-I, Phospholipid, and Factor H-related Proteins J. Biol. Chem., July 26, 1996; 271(30): 18054 - 18060. [Abstract] [Full Text] [PDF]

				A. Smith, J. Esko, and S. Hajduk Killing of trypanosomes by the human haptoglobin-related protein Science, April 14, 1995; 268(5208): 284 - 286. [Abstract] [PDF]

				J. Drain, J. R. Bishop, and S. L. Hajduk Haptoglobin-related Protein Mediates Trypanosome Lytic Factor Binding to Trypanosomes J. Biol. Chem., August 3, 2001; 276(32): 30254 - 30260. [Abstract] [Full Text] [PDF]