Insight into the mechanism of trypanosome lytic factor-1 killing of Trypanosoma brucei brucei
Insight into the mechanism of trypanosome lytic factor-1 killing of Trypanosoma brucei brucei
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DOI：
10.1016/s0166-6851(01)00361-9
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发表时间：
2001-11-01
影响因子：
1.5
通讯作者：
Hajduk, SL
中科院分区：
文献类型：
--
作者：
Bishop, JR;Shimamura, M;Hajduk, SL
几乎世纪以来，人们都知道正常人血清可以裂解细胞外血液寄生虫布氏锥虫。这一过程是人类血清中一种称为锥虫溶解因子（TLF）的非免疫杀伤因子的结果。在这项工作中，我们证明了T. B.在体外，亲脂性铁螯合剂LI、亲脂性抗氧化剂DPPD和蛋白酶抑制剂antipain和E64抑制了锥虫溶解因子-1（TLF-1）对布氏杆菌的作用。因此，TLF-1的杀伤可能需要铁，氧化剂，丝氨酸和半胱氨酸蛋白酶。此外，我们证明了TLF-1介导的裂解导致T。通过DPPD、弱碱和人触珠蛋白抑制的反应，将其转化为布鲁氏菌脂质。我们假设TLF-1裂解需要锥虫内的细胞内因素，包括高细胞内H2 O2和高多烯脂质浓度，溶酶体酸化和蛋白酶，以及细胞内铁源。所呈现的数据支持以下假设：这些因子与溶酶体内的TLF-1的组合导致溶酶体膜破裂、溶酶体内容物的释放以及随后的细胞自身消化。(C)2001 Elsevier Science B. V.保留所有权利。
It has been known for almost a century that normal human serum can lyse the extracellular blood parasite Trypanosoma brucei brucei. This process is a result of a non-immune killing factor in human sera known as trypanosome lytic factor (TLF). In this work, we demonstrate that killing of T. b. brucei by trypanosome lytic factor-1 (TLF-1) in vitro is inhibited by the lipophyllic iron chelator, LI, the lipophyllic antioxidant DPPD, and the protease inhibitors antipain and E64. Thus TLF-1 killing likely requires iron, oxidants, and serine and cysteine proteases. Furthermore, we demonstrate that TLF-1 mediated lysis causes measurable peroxidation in T. brucei lipids via a reaction that is inhibited by DPPD, weak bases, and human haptoglobin. We hypothesize that TLF-1 lysis requires intracellular factors within the trypanosome including high intracellular H2O2 and high polyenoic lipid concentrations, lysosomal acidification and proteases, and intracellular iron sources. The data presented supports the hypothesis that the combination of these factors with TLF-1 inside the lysosome results in lysosomal membrane breakdown, release of the lysosomal contents, and subsequent autodigestion of the cell. (C) 2001 Elsevier Science B.V. All rights reserved.