Chen Zhizhong, Qing Jilin, Hu Lihua
Department of Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Laboratory, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
J Huazhong Univ Sci Technolog Med Sci. 2012 Feb;32(1):9-16. doi: 10.1007/s11596-012-0002-1. Epub 2012 Jan 27.
T cell immunoglobulin mucin (TIM) family plays a key role in regulating immune responses. In this study, the interactions of human TIM family with apoptotic cells were evaluated in order to provide a foundation for further study on the roles of human TIM genes in apoptosis. Nine kinds of pEGFP-N1 eukaryotic expression vectors containing different lengths of the three members of human TIM genes for the expression of TIM-EGFP and the vectors for the expression of TIM-Fc fusion proteins were constructed. It was found that human TIM proteins could recognize and bind to apoptotic cells directly, but not to viable cells. The interactions of sTIM-1-EGFP, sTIM-3-EGFP and sTIM-4-EGFP with apoptotic cells were blocked by TIM-1-Ig, TIM-3-Ig and TIM-4-Ig fusion proteins respectively. In addition, human TIM proteins mediated the recognition of apoptotic cells and bound to apoptotic cells directly via the IgV domains. In conclusion, the TIM family may play a key role in the regulation of apoptosis. Our data also suggest that human TIM proteins probably serve as novel proteins for the detection of the early cellular apoptosis.
T细胞免疫球蛋白黏蛋白（TIM）家族在调节免疫反应中起关键作用。在本研究中，评估了人类TIM家族与凋亡细胞的相互作用，以便为进一步研究人类TIM基因在凋亡中的作用奠定基础。构建了9种含不同长度人类TIM基因三个成员的pEGFP-N1真核表达载体用于TIM-EGFP的表达，以及用于TIM-Fc融合蛋白表达的载体。发现人类TIM蛋白可直接识别并结合凋亡细胞，但不与活细胞结合。sTIM-1-EGFP、sTIM-3-EGFP和sTIM-4-EGFP与凋亡细胞的相互作用分别被TIM-1-Ig、TIM-3-Ig和TIM-4-Ig融合蛋白阻断。此外，人类TIM蛋白介导对凋亡细胞的识别并通过IgV结构域直接与凋亡细胞结合。总之，TIM家族可能在凋亡调节中起关键作用。我们的数据还表明，人类TIM蛋白可能作为检测早期细胞凋亡的新型蛋白。
