Effects of Heparin Administration on Trypanosoma brucei gambiense Infection in Rats

We examined whether heparin administration influences in vivo trypanosome proliferation in infected rats. Administration of heparin every 8 hr via cardiac catheter inhibited growth of Trypanosoma brucei gambiense and prolonged survival of treated rats. Heparin administration increased lipoprotein lipase activity, high-density lipoprotein (HDL) concentration in the blood, and haptoglobin messenger RNA content of the liver. The presence of heparin in culture media did not directly affect proliferation of trypanosomes in vitro. However, the addition of plasma from infected rats treated with heparin to culture media decreased the number of trypanosomes. This effect was decreased by incubating the trypanosomes with benzyl alcohol, a known inhibitor of receptor-mediated endocytosis of lipoprotein. These data suggested that heparin administration reduced the number of trypanosomes in infected rats. Trypanosome lytic factor, a HDL and haptoglobin-related protein, protects humans and some animals from infection by Trypanosoma brucei brucei. In rats, increases in HDL and haptoglobin may affect the proliferation of T. b. gambiense.

[1]  M. Igarashi,et al.  Development of Neospora caninum Cultured with Human Serum In Vitro and In Vivo , 2005, The Journal of parasitology.

[2]  S. Yamasaki,et al.  Differential effects of interferon-gamma on production of trypanosome-derived lymphocyte-triggering factor by Trypanosoma brucei gambiense and Trypanosoma brucei brucei. , 2004, The Journal of parasitology.

[3]  C. Blondin,et al.  Heparin inhibits lipopolysaccharide (LPS) binding to leukocytes and LPS-induced cytokine production. , 2003, Journal of biomedical materials research. Part A.

[4]  R. Brasseur,et al.  Apolipoprotein L-I is the trypanosome lytic factor of human serum , 2003, Nature.

[5]  M. Shi,et al.  Experimental African trypanosomiasis: IFN‐γ mediates early mortality , 2003 .

[6]  K. Sung,et al.  Upregulation of Haptoglobin in Reactive Astrocytes after Transient Forebrain Ischemia in Rats , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  S. Black,et al.  Serum xanthine oxidase: origin, regulation, and contribution to control of trypanosome parasitemia. , 2002, Antioxidants & redox signaling.

[8]  S. Hajduk,et al.  Haptoglobin-related Protein Mediates Trypanosome Lytic Factor Binding to Trypanosomes* , 2001, The Journal of Biological Chemistry.

[9]  M. Yamada,et al.  Over-expression of GAPDH induces apoptosis in COS-7 cells transfected with cloned GAPDH cDNAs. , 1999, Neuroreport.

[10]  D. Remick,et al.  Low molecular weight heparin is associated with greater cytokine production in a stimulated whole blood model. , 1998, Shock.

[11]  N. Ohta,et al.  Continuous growth of bloodstream forms of Trypanosoma brucei brucei in an axenic culture system containing a low concentration of serum. , 1998, The Southeast Asian journal of tropical medicine and public health.

[12]  J. Grootenhuis,et al.  The trypanocidal Cape buffalo serum protein is xanthine oxidase , 1997, Infection and immunity.

[13]  S. Hajduk,et al.  Mechanism of resistance of African trypanosomes to cytotoxic human HDL , 1997, Nature.

[14]  S. Hajduk,et al.  Identification of haptoglobin as a natural inhibitor of trypanocidal activity in human serum. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Hamsten,et al.  Lipoprotein lipase mass and activity in plasma and their increase after heparin are separate parameters with different relations to plasma lipoproteins. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[16]  J. Seed,et al.  Mechanism of lysis of Trypanosoma brucei gambiense by human serum. , 1994, The Journal of parasitology.

[17]  K. Polonsky,et al.  Heparin-induced lipolysis in hypertriglyceridemic subjects results in the formation of atypical HDL particles. , 1994, Journal of lipid research.

[18]  D. Goldberg,et al.  Effect of chronic heparin administration on serum lipolytic activity and some aspects of lipid metabolism. , 1990, Biochimica et biophysica acta.

[19]  J. Philippot,et al.  Effects of benzyl alcohol on transferrin and low density lipoprotein receptor mediated endocytosis in leukemic guinea pig B lymphocytes , 1990, FEBS letters.

[20]  M. Burstein,et al.  Rapid method for the isolation of two purified subfractions of high density lipoproteins by differential dextran sulfate-magnesium chloride precipitation. , 1989, Biochimie.

[21]  J. Swaney,et al.  Effects of heparin-induced lipolytic activity on the structure of rat high-density lipoprotein. , 1989, Biochimica et biophysica acta.

[22]  S. M. Lanham.  Separation of Trypanosomes from the Blood of Infected Rats and Mice by Anion-exchangers , 1968, Nature.