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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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Morphological  characteristics of temperature  dependent TNF-α–mediated  lysis of bloodstream forms of  T. brucei. Lysis assays were  performed for 5 h at 30° and  21°C as described in Materials  and Methods, using a TNF-α  concentration of 104 U/ml. (a)  At 30°C no background lysis  was observed in the absence  of TNF-α. (b). In the presence of the cytokine, most  parasites were lysed after  the 5-h incubation period.  Remaining cells had a ghostlike appearance (arrow) or  showed an abnormal swollen  morphology (arrowhead).  At 21°C, no signs of altered  morphology or lysis were observed in the absence (c) or  presence (d) of TNF-α. Bar,  20 μm.
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Figure 7: Morphological characteristics of temperature dependent TNF-α–mediated lysis of bloodstream forms of T. brucei. Lysis assays were performed for 5 h at 30° and 21°C as described in Materials and Methods, using a TNF-α concentration of 104 U/ml. (a) At 30°C no background lysis was observed in the absence of TNF-α. (b). In the presence of the cytokine, most parasites were lysed after the 5-h incubation period. Remaining cells had a ghostlike appearance (arrow) or showed an abnormal swollen morphology (arrowhead). At 21°C, no signs of altered morphology or lysis were observed in the absence (c) or presence (d) of TNF-α. Bar, 20 μm.

Mentions: TNF-α–induced morphological alterations which preceded lysis could only be observed by light microscopy when incubation temperatures above 26°C were used. At 30°C in the absence of TNF-α, virtually no morphological changes were observed after a 5 h incubation period (Fig. 7 a). However, in the presence of TNF-α, a large number of cells were lysed, and most of the remaining cells showed a clearly altered swollen morphology (Fig. 7 b). When incubations were performed at 21°C, no morphological differences were observed between the cells incubated in the absence and presence of TNF-α, as shown in Fig. 7, c and d, respectively.


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)

Morphological  characteristics of temperature  dependent TNF-α–mediated  lysis of bloodstream forms of  T. brucei. Lysis assays were  performed for 5 h at 30° and  21°C as described in Materials  and Methods, using a TNF-α  concentration of 104 U/ml. (a)  At 30°C no background lysis  was observed in the absence  of TNF-α. (b). In the presence of the cytokine, most  parasites were lysed after  the 5-h incubation period.  Remaining cells had a ghostlike appearance (arrow) or  showed an abnormal swollen  morphology (arrowhead).  At 21°C, no signs of altered  morphology or lysis were observed in the absence (c) or  presence (d) of TNF-α. Bar,  20 μm.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Morphological characteristics of temperature dependent TNF-α–mediated lysis of bloodstream forms of T. brucei. Lysis assays were performed for 5 h at 30° and 21°C as described in Materials and Methods, using a TNF-α concentration of 104 U/ml. (a) At 30°C no background lysis was observed in the absence of TNF-α. (b). In the presence of the cytokine, most parasites were lysed after the 5-h incubation period. Remaining cells had a ghostlike appearance (arrow) or showed an abnormal swollen morphology (arrowhead). At 21°C, no signs of altered morphology or lysis were observed in the absence (c) or presence (d) of TNF-α. Bar, 20 μm.
Mentions: TNF-α–induced morphological alterations which preceded lysis could only be observed by light microscopy when incubation temperatures above 26°C were used. At 30°C in the absence of TNF-α, virtually no morphological changes were observed after a 5 h incubation period (Fig. 7 a). However, in the presence of TNF-α, a large number of cells were lysed, and most of the remaining cells showed a clearly altered swollen morphology (Fig. 7 b). When incubations were performed at 21°C, no morphological differences were observed between the cells incubated in the absence and presence of TNF-α, as shown in Fig. 7, c and d, respectively.

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