ABSTRACT
Polyamines are essential for proliferation of Trypanosoma brucei brucei, and feeding rats polyamine-deficient chow (PDC) decreases their blood polyamine concentrations. Proliferation of T. b. brucei (IL-tat 1.4 strain) (IL) is not restrained within PDC-fed rats. However, symptoms of IL-infected rats such as anemia decrease by PDC feeding. We reported cytokine and nitric oxide (NO) production of T. b. gambiense (Wellcome strain [WS])-infected rats were affected by PDC feeding, and WS proliferation was restrained. Therefore, we investigated whether the change in production of cytokines and NO by PDC feeding affects IL proliferation and decreases symptoms in vivo. In IL-infected PDC-fed rats, NO, interleukin (IL)-12, and tumor necrosis factor-alpha production increased while interferon-gamma and IL-10 decreased compared to normal chow-fed rats. IL proliferation was restrained by NO production when it was co-cultured with spleen cells harvested from uninfected rats. In contrast, IL proliferation in infected rats was not changed by PDC feeding, although NO production was increased. The results suggest that changes in cytokines and NO production in IL-infected rats by PDC feeding have little influence on IL proliferation. However, they may serve to decrease symptoms.
Subject(s)
Cytokines/blood , Nitric Oxide/biosynthesis , Polyamines/blood , Trypanosoma brucei brucei/growth & development , Trypanosomiasis, African/parasitology , Anemia/prevention & control , Animal Feed , Animals , Cells, Cultured , Coculture Techniques , Cytokines/genetics , Erythrocytes/chemistry , Erythrocytes/immunology , Erythrocytes/parasitology , Male , Nitric Oxide/blood , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Ornithine Decarboxylase/genetics , Ornithine Decarboxylase/metabolism , Osmotic Fragility , Polyamines/administration & dosage , Polyamines/metabolism , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Spleen/cytology , Spleen/immunology , Spleen/metabolism , Trypanosoma brucei brucei/immunology , Trypanosoma brucei brucei/metabolism , Trypanosomiasis, African/diet therapy , Trypanosomiasis, African/immunologyABSTRACT
We studied the effects of polyamines, which are necessary for proliferation and antioxidation in Trypanosoma brucei gambiense Wellcome strain (WS) and Trypanosoma brucei brucei ILtat 1.4 strain (IL). No difference was found in activity of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis in trypanosomes, in both strains maintained in vitro; higher (P < 0.05) ODC values were found in IL in vivo. However, WS in vivo exhibited higher proliferation rates with higher spermidine content and decreased host survival times than IL. The in vitro proliferation and polyamine contents of WS increased with the addition of polyamine to the 1-difluoromethylornithine culture medium, but not IL. These results suggested that WS uses extracellular polyamine for proliferation. In the in vitro culture, WS was less tolerant of hydrogen peroxide (oxidative stress) than IL, and malondialdehyde levels in WS were higher than in IL. The expression of trypanothione synthetase mRNA in WS in vitro was higher than in IL. These results suggest that IL is dependent on the synthesis of polyamines for proliferation and reduction of oxidative stress, whereas WS is dependent on the uptake of extracellular polyamines. A thorough understanding of the differences in the metabolic capabilities of various trypanosomes is important for the design of more effective medical treatments.
