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Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.

Magez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E, de Baetselier P - J. Cell Biol. (1997)

Bottom Line: The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity.Anti-TNF-alpha treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity.These data suggest that in the mammalian host, TNF-alpha is involved in the growth control of T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Belgium.

ABSTRACT
Trypanosoma brucei is lysed by tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-alpha-gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity. TNF-alpha specific lysis is prevented when lysis assays are performed at a temperature <26 degrees C, despite uptake of the cytokine. Inhibition of lysis is also observed when a lysosomotropic agent is added during the first 2 h of incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when isolated during the peak of parasitaemia. Lysis is not observed with early infection stage parasites or procyclic (insect-specific) forms. Anti-TNF-alpha treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity. These data suggest that in the mammalian host, TNF-alpha is involved in the growth control of T. brucei.

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Inhibition of TNFα–mediated trypanolysis by  NH4Cl. Lysis assays were  carried out as described in  Materials and Methods. (a)  NH4Cl effects on lysis of T.  brucei as function of concentration. Trypanosomes were  incubated at 30°C in the presence of 104 U/ml TNF-α and  different concentrations  NH4Cl. (b) Effects of NH4Cl  on trypanolysis as function of  addition after preincubation  of parasites with TNF-α.  Trypanosomes were incubated for 5 h at 30°C in the  presence of 104 U/ml TNF-α.  Every hour NH4Cl was  added to one sample to a final concentration of 1 mM.  The percentage of lysis inhibition was calculated compared to a  control lysis of 104 U/ml in the absence of NH4Cl.
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Figure 9: Inhibition of TNFα–mediated trypanolysis by NH4Cl. Lysis assays were carried out as described in Materials and Methods. (a) NH4Cl effects on lysis of T. brucei as function of concentration. Trypanosomes were incubated at 30°C in the presence of 104 U/ml TNF-α and different concentrations NH4Cl. (b) Effects of NH4Cl on trypanolysis as function of addition after preincubation of parasites with TNF-α. Trypanosomes were incubated for 5 h at 30°C in the presence of 104 U/ml TNF-α. Every hour NH4Cl was added to one sample to a final concentration of 1 mM. The percentage of lysis inhibition was calculated compared to a control lysis of 104 U/ml in the absence of NH4Cl.

Mentions: The TEM analysis with TNF-α–gold particles strongly suggests that the particles reach a lysosome-like compartment as a final destination. Hence, the influence of pH elevation on trypanolysis was analyzed. As shown in Fig. 9 a, the presence of NH4Cl during TNF-α incubations resulted clearly in a dose-dependent inhibition of lysis. Maximal inhibitions of ∼90% were recorded using concentrations of 1 mM of NH4Cl or higher. Inhibition of TNF-α–mediated lysis by 1 mM of NH4Cl was even recorded when the compound was added 2 h after incubation with TNF-α (Fig. 9 b). Addition of NH4Cl after 3 h of TNF-α treatment did not result in a substantial inhibition of lysis. Hence, an acidic environment at the destination site of internalized TNF-α appears to be required for TNF-α–mediated lysis.


Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.

Magez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E, de Baetselier P - J. Cell Biol. (1997)

Inhibition of TNFα–mediated trypanolysis by  NH4Cl. Lysis assays were  carried out as described in  Materials and Methods. (a)  NH4Cl effects on lysis of T.  brucei as function of concentration. Trypanosomes were  incubated at 30°C in the presence of 104 U/ml TNF-α and  different concentrations  NH4Cl. (b) Effects of NH4Cl  on trypanolysis as function of  addition after preincubation  of parasites with TNF-α.  Trypanosomes were incubated for 5 h at 30°C in the  presence of 104 U/ml TNF-α.  Every hour NH4Cl was  added to one sample to a final concentration of 1 mM.  The percentage of lysis inhibition was calculated compared to a  control lysis of 104 U/ml in the absence of NH4Cl.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139880&req=5

Figure 9: Inhibition of TNFα–mediated trypanolysis by NH4Cl. Lysis assays were carried out as described in Materials and Methods. (a) NH4Cl effects on lysis of T. brucei as function of concentration. Trypanosomes were incubated at 30°C in the presence of 104 U/ml TNF-α and different concentrations NH4Cl. (b) Effects of NH4Cl on trypanolysis as function of addition after preincubation of parasites with TNF-α. Trypanosomes were incubated for 5 h at 30°C in the presence of 104 U/ml TNF-α. Every hour NH4Cl was added to one sample to a final concentration of 1 mM. The percentage of lysis inhibition was calculated compared to a control lysis of 104 U/ml in the absence of NH4Cl.
Mentions: The TEM analysis with TNF-α–gold particles strongly suggests that the particles reach a lysosome-like compartment as a final destination. Hence, the influence of pH elevation on trypanolysis was analyzed. As shown in Fig. 9 a, the presence of NH4Cl during TNF-α incubations resulted clearly in a dose-dependent inhibition of lysis. Maximal inhibitions of ∼90% were recorded using concentrations of 1 mM of NH4Cl or higher. Inhibition of TNF-α–mediated lysis by 1 mM of NH4Cl was even recorded when the compound was added 2 h after incubation with TNF-α (Fig. 9 b). Addition of NH4Cl after 3 h of TNF-α treatment did not result in a substantial inhibition of lysis. Hence, an acidic environment at the destination site of internalized TNF-α appears to be required for TNF-α–mediated lysis.

Bottom Line: The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity.Anti-TNF-alpha treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity.These data suggest that in the mammalian host, TNF-alpha is involved in the growth control of T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Belgium.

ABSTRACT
Trypanosoma brucei is lysed by tumor necrosis factor-alpha (TNF-alpha) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-alpha-gold particles are endocytosed via coated pits and vesicles and are directed towards lysosome-like digestive organelles. The specific uptake of the cytokine by the parasite results in a developmentally regulated loss of osmoregulatory capacity. TNF-alpha specific lysis is prevented when lysis assays are performed at a temperature <26 degrees C, despite uptake of the cytokine. Inhibition of lysis is also observed when a lysosomotropic agent is added during the first 2 h of incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when isolated during the peak of parasitaemia. Lysis is not observed with early infection stage parasites or procyclic (insect-specific) forms. Anti-TNF-alpha treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity. These data suggest that in the mammalian host, TNF-alpha is involved in the growth control of T. brucei.

Show MeSH
Related in: MedlinePlus