调节T淋巴细胞中信号传递的第二个信使周期性ADP-ribose
A H Guse1, C P da Silva, I Berg
1Department of Enzyme Chemistry, Institute of Physiological Chemistry, University of Hamburg, Germany. guse@uke.uni-hamburg.de
Nature
|March 17, 1999
概括
循环ADP-ribose (cADPR) 在T淋巴细胞中起到关键的第二信使作用,调节信号传递和T细胞激活. 这项研究证实了cADPR的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 已知循环ADP-ribose (cADPR) 能够在真核细胞中调动离子.
- 它作为T淋巴细胞中的第二信使的作用仍然不完全理解.
- T细胞激活涉及复杂的信号通路,包括调动.
研究的目的:
- 为了在T淋巴细胞中建立循环ADP-核糖 (cADPR) 作为第二信使.
- 研究cADPR在T细胞受体/CD3 (TCR/CD3) 复合介导信号传递中的作用.
- 阐明T细胞中cADPR作用的分子机制.
主要方法:
- 高性能液体色谱 (HPLC) 用于测量细胞内cADPR水平.
- 通过TCR/CD3复合体进行T细胞刺激.
- 使用cADPR抗剂来评估信号抑制.
- 对T细胞增殖和激活标记物的分析 (CD25,HLA-DR).
- 使用 [3H] 氨酸的放射性结试验来研究氨酸受体相互作用.
主要成果:
- TCR/CD3刺激激活ADP-ribosyl循环酶,从而增加细胞内cADPR水平.
- 增加的cADPR与持续的信号传递和T细胞激活有因果关系.
- cADPR对抗剂抑制TCR/CD3诱导的信号传递,增殖和激活标志物的表达.
- 3型氨酸受体是cADPR的标,在T细胞中表达.
- cADPR直接调节3型氨酸受体的活性.
结论:
- 循环ADP-核糖 (cADPR) 是人类T细胞中重要的第二信使.
- 涉及3型氨酸受体的cADPR/信号通路对于T细胞激活至关重要.
- 这一途径代表了调节T细胞反应的潜在治疗标.
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