Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.
Specific uptake of tumor necrosis factor-alpha is involved in growth control of Trypanosoma brucei.
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DOI：
10.1083/jcb.137.3.715
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发表时间：
1997-05-05
期刊：
影响因子：
--
通讯作者：
de Baetselier P
中科院分区：
文献类型：
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作者：
Magez S;Geuskens M;Beschin A;del Favero H;Verschueren H;Lucas R;Pays E;de Baetselier P
布氏锥虫以剂量依赖性方式被肿瘤坏死因子-α (TNF-α) 裂解，涉及细胞因子与寄生虫鞭毛袋中存在的锥虫糖蛋白的特异性结合。 TNF-α-金颗粒通过包被的凹坑和囊泡被内吞，并被引导至溶酶体样消化细胞器。寄生虫对细胞因子的特异性摄取导致发育调节的渗透压调节能力丧失。当裂解测定在 <26°C 的温度下进行时，尽管细胞因子被吸收，TNF-α 特异性裂解仍会被阻止。当在孵育的前 2 小时内添加溶酶体剂时，也观察到裂解的抑制。单形性和多形性锥虫都会被裂解，但只有在寄生虫血症高峰期分离时才会被裂解。早期感染阶段寄生虫或前循环（昆虫特异性）形式未观察到裂解。对布氏锥虫感染的小鼠进行抗 TNF-α 治疗后，发现血液循环、脾脏、淋巴结和腹膜腔中的寄生虫血症急剧增加。这些数据表明，在哺乳动物宿主中，TNF-α 参与布氏锥虫的生长控制。
Trypanosoma brucei is lysed by tumor necrosis factor-α (TNF-α) in a dose-dependent way, involving specific binding of the cytokine to a trypanosomal glycoprotein present in the flagellar pocket of the parasite. TNF-α–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-α specific lysis is prevented when lysis assays are performed at a temperature <26°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-α 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-α is involved in the growth control of T. brucei.