Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Jul;75(7):3450–3454. doi: 10.1073/pnas.75.7.3450

Identification of the trypanocidal factor in normal human serum: high density lipoprotein.

M R Rifkin
PMCID: PMC392795  PMID: 210461

Abstract

The differentiation of Trypanosoma brucei from T. rhodesiense, the causative agent of human sleeping sickness, depends on their relative sensitivities to the cytotoxic effects of normal human serum. The molecule responsible for the specific lysis of T. brucei has now been isolated. Serum lipoproteins were fractionated and purified by ultracentrifugal flotation and chromatography on Bio-Gel A-5m. Trypanocidal activity was recovered in the high density lipoprotein fraction (density, 1.063-1.216 g/ml). Contamination by other serum proteins was checked by crossed immunoelectrophoresis and sodium dodecyl sulfate/acrylamide gel electrophoresis. Only a trace of beta-lipoprotein was found. The trypanocidal activity of pure human high density lipoprotein was identical to that of unfractionated serum when the following were tested: (i) time course of in vitro lysis of T. bruceli; (ii) in vivo destruction of T. brucei; (iii) relative resistance of T. rhodesiense to lysis. Rat or rabbit high density lipoprotein had no trypanocidal activity. Identification of the trypanocidal factor as high density lipoprotein was confirmed by the finding that serum from patients with Tangier disease, an autosomal recessive disorder characterized by a severe deficiency of high density lipoprotein, had no trypanocidal activity.

Full text

PDF
3450

Images in this article

3452Image
on p.3452
3452Image
on p.3452

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bienz K. Uber die Züchtbarkeit von Trypanosoma brucei und dessen Vermehrungsfähigkeit in virusinfizierten Wirten. Acta Trop. 1968;25(1):39–71. [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. Familial hypercholesterolemia: defective binding of lipoproteins to cultured fibroblasts associated with impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Proc Natl Acad Sci U S A. 1974 Mar;71(3):788–792. doi: 10.1073/pnas.71.3.788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bruckdorfer K. R., Demel R. A., De Gier J., van Deenen L. L. The effect of partial replacements of membrane cholesterol by other steroids on the osmotic fragility and glycerol permeability of erythrocytes. Biochim Biophys Acta. 1969 Jul 15;183(2):334–345. doi: 10.1016/0005-2736(69)90089-3. [DOI] [PubMed] [Google Scholar]
  4. Cross G. A. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology. 1975 Dec;71(3):393–417. doi: 10.1017/s003118200004717x. [DOI] [PubMed] [Google Scholar]
  5. Hawking F. The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. I. Analysis of the composition of trypanosome strains. Trans R Soc Trop Med Hyg. 1976;70(5-6):504–512. doi: 10.1016/0035-9203(76)90138-3. [DOI] [PubMed] [Google Scholar]
  6. Hawking F. The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. I. Analysis of the composition of trypanosome strains. Trans R Soc Trop Med Hyg. 1976;70(5-6):504–512. doi: 10.1016/0035-9203(76)90138-3. [DOI] [PubMed] [Google Scholar]
  7. Herbert W. J., Lumsden W. H. Trypanosoma brucei: a rapid "matching" method for estimating the host's parasitemia. Exp Parasitol. 1976 Dec;40(3):427–431. doi: 10.1016/0014-4894(76)90110-7. [DOI] [PubMed] [Google Scholar]
  8. Jackson R. L., Gotto A. M., Stein O., Stein Y. A comparative study on the removal of cellular lipids from Landschütz ascites cells by human plasma apolipoproteins. J Biol Chem. 1975 Sep 25;250(18):7204–7209. [PubMed] [Google Scholar]
  9. LEVY R. I., FREDRICKSON D. S. HETEROGENEITY OF PLASMA HIGH DENSITY LIPOPROTEINS. J Clin Invest. 1965 Mar;44:426–441. doi: 10.1172/JCI105156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Mendez Y., Honigberg B. M. Infectivity of Trypanosoma brucei-subgroup flagellates maintained in culture. J Parasitol. 1972 Dec;58(6):1122–1136. [PubMed] [Google Scholar]
  12. Miller N. E., Weinstein D. B., Carew T. E., Koschinsky T., Steinberg D. Interaction between high density and low density lipoproteins uptake and degradation by cultured human fibroblasts. J Clin Invest. 1977 Jul;60(1):78–88. doi: 10.1172/JCI108772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Neville D. M., Jr Molecular weight determination of protein-dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. J Biol Chem. 1971 Oct 25;246(20):6328–6334. [PubMed] [Google Scholar]
  14. Rickman L. R., Robson J. The testing of proven Trypanosoma brucei and T. rhodesiense strains by the blood incubation infectivity test. Bull World Health Organ. 1970;42(6):911–916. [PMC free article] [PubMed] [Google Scholar]
  15. Rudel L. L., Lee J. A., Morris M. D., Felts J. M. Characterization of plasma lipoproteins separated and purified by agarose-column chromatography. Biochem J. 1974 Apr;139(1):89–95. doi: 10.1042/bj1390089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schlager S. I., Ohanian S. H. Correlation between lipid synthesis in tumor cells and their sensitivity to humoral immune attack. Science. 1977 Aug 19;197(4305):773–776. doi: 10.1126/science.196331. [DOI] [PubMed] [Google Scholar]
  17. Stein O., Stein Y. The removal of cholesterol from Landschütz ascites cells by high-density apolipoprotein. Biochim Biophys Acta. 1973 Nov 29;326(2):232–244. doi: 10.1016/0005-2760(73)90249-x. [DOI] [PubMed] [Google Scholar]
  18. Tall A. R., Small D. M. Solubilisation of phospholipid membranes by human plasma high density lipoproteins. Nature. 1977 Jan 13;265(5590):163–164. doi: 10.1038/265163a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES