LYSIS OF TRYPANOSOMA BRUCEI BY HUMAN SERUM

人血清裂解布氏锥虫

• 批准号: 6169837
• 负责人: Stephen Tomlinson
• 金额: $ 9.88万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169837
• 关键词: SDS polyacrylamide gel electrophoresis; Trypanosoma; Trypanosoma brucei rhodesiense; affinity chromatography; apoptosis; binding proteins; cytolysis; electron microscopy; enzyme activity; gel electrophoresis; gene expression; high density lipoproteins; human tissue; immunoprecipitation; interleukin 1; laboratory mouse; oxidative stress; peroxidases; peroxidation; protein structure function; protozoal toxin; receptor sensitivity; serum; trypanosomiasis

Trypanosoma brucei brucei, unlike the human pathogens Tau beta rhodesiense and Tau gambiense, is lysed by human serum. Sensitivity to human serum is the only method which allows distinction between the cattle and human African trypanosomes. We have identified two distinct trypanolytic fractions in normal human serum (NHS) which differ physically, biochemically and with regard to their inhibition by serum factors. Significantly, an HDL-like trypanolytic factor (TLF1) described by others is not active in NHS, and only becomes lytic upon inhibitor removal during isolation procedures. It is proposed to characterize the more physiologically relevant lytic factor in human serum, and to determine the mechanism(s) by which parasites are killed by both factors. Data indicates that a mechanism of lysis may involve oxidative stress and subsequent programmed cell death, and these possibilities will be tested directly. This work may open new perspectives for the chemotherapy of trypanosomiasis. Understanding of the mechanisms of cytotoxicity and the affected metabolic pathways may provide new approaches for development of specific drugs.

与人类病原体Tau Beta不同，Brucei Brucei锥虫 Rhodesiense和Tau gambiense被人血清裂解。对 人血清是唯一可以区分的方法 牛和人类非洲锥虫。我们已经确定了两个不同的 正常人血清（NHS）中的锥虫分数不同 在身体上，生化和血清抑制作用 因素。 值得注意的是，HDL样锥虫液化因子（TLF1） 他人描述的NHS在NHS中不活跃，只在 在隔离程序中去除抑制剂。 提议 表征人类在生理上相关的裂解因子中的特征 血清，并确定寄生虫被杀死的机制 这两个因素。 数据表明裂解机制可能涉及 氧化应激和随后的编程细胞死亡，这些 可能性将直接测试。 这项工作可能会开放 锥虫病的化学疗法的观点。理解 细胞毒性的机制和受影响的代谢途径可能 为开发特定药物提供新的方法。