HIGH-DENSITY-LIPOPROTEIN-INDEPENDENT KILLING OF TRYPANOSOMA-BRUCEI BY HUMAN SERUM

HIGH-DENSITY-LIPOPROTEIN-INDEPENDENT KILLING OF TRYPANOSOMA-BRUCEI BY HUMAN SERUM
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DOI:
10.1016/0166-6851(95)00019-w
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发表时间:
1995-03-01
影响因子:
1.5
通讯作者:
NUSSENZWEIG, V
NUSSENZWEIG, V
中科院分区:
医学4区
文献类型:
--
作者:
TOMLINSON, S;JANSEN, AM;NUSSENZWEIG, V

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牛病原体布氏锥虫在形态上与人类病原体布氏锥虫没有区别。罗德西亚和 T.b.冈比亚人。然而,与人类病原体不同的是,T.b.布氏杆菌可被正常人血清 (NHS) 裂解。 NHS 中的锥虫分解因子与高密度脂蛋白 (HDL) 共同纯化,但其确切性质尚不清楚。使用新的基于荧光的活力测定来评估 T.b.杀死布氏杆菌后,我们发现两名丹吉尔病患者的 HDL 缺乏血清与 NHS 一样具有锥虫分解作用。通过密度超速离心对丹吉尔血清进行分级显示,该活性仅存在于脂蛋白耗尽的级分中。 Tangier 和 NHS 也进行了分子筛色谱分析,活性曲线相同。 T. brucei(但不是 T. rhodesense)的裂解组分出现在 100-600 kDa 和 > 1000 kDa 的两个不同峰下。两个峰均不与通过胆固醇滴定确定的主要血清脂蛋白的位置重合。高分子质量峰不含 HDL 相关载脂蛋白-A1。此外,我们没有发现纯化的载脂蛋白 A1 或 J 对锥虫有溶解作用。我们得出的结论是,人血清对布氏锥虫的杀灭作用可以独立于 HDL。
The cattle pathogen Trypanosoma brucei brucei is morphologically indistinguishable from the human pathogens T.b. rhodesiense and T.b. gambiense. However, unlike the human pathogens, T.b. brucei is lysed by normal human serum (NHS). The trypanolytic factor in NHS co-purifies with high-density lipoproteins (HDL), but its precise nature is unknown. Using a new fluorescence-based viability assay to assess T.b. brucei killing, we find that the HDL-deficient sera from two patients with Tangier disease are as trypanolytic as NHS. Fractionation of the Tangier sera by density ultracentrifugation revealed that the activity resides only in lipoprotein-depleted fractions. Tangier and NHS were also subjected to molecular sieving chromatography, and the activity profiles were identical. Lytic fractions to T. brucei (but not to T. rhodesiense) appeared under two distinct peaks of 100-600 kDa and > 1000 kDa. Neither peak coincided with the position of the major serum lipoproteins, as determined by cholesterol titrations. The high-molecular-mass peak did not contain the HDL-associated apolipoprotein-A1. Further, we did not find that purified apolipoproteins A1 or J are lytic for the trypanosomes. We conclude that the killing of T. brucei by human serum can be independent of HDL.