Mechanisms of pyknotic cell death in vivo and their biological significance

体内固缩细胞死亡机制及其生物学意义

基本信息

批准号：
10470002
负责人：
ITOH Tsunetoshi
金额：
$ 2.5万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470002/
关键词：
Thymus Thymocytes Differentiation Selection Clonal deletion Microenvironment Apoptosis Cell death

项目摘要

Most of programmed cell deaths during the developmental processes have been considered to be apoptosis accompanying DNA fragmentation. We have precisely examined thymocyte deaths and B cell deaths in the germinal centers, i.e., "cell deaths" in situ, and found that they are pyknosis with heavy nuclear condensation without DNA fragmentation ; they are totally distinct from typical apoptosis, which is characterized by DNA fragmentation and marginal chromatin condensation. We re-evaluated various cell deaths in vivo, and rectategorize those in situ cell deaths on the basis of the novel point of view, in order to analyze the mechanisms of the new type of cell deaths, pyknosis, and to delineate their biological significance.We analyzed morphologically cell deaths in vivo during the development, especially the cell deaths observed in the interdigital tissues and found that the cell deaths in this tissue did not accompany DNA fragmentation, and accordingly, we concluded that they are not apoptosis. Massive cell deaths triggered by anti-CD3 antibody treatment have been found typical apoptosis, because they fragmented DNA at much earlier stages when morphological changes could be observed.We have undertaken a project to develop a monoclonal antibody to detect the earliest sign of pyknosis, a surface antigen of dying thymocytes to be recognized by macrophages for ingestion. This project has been underway, and will be pursued until the development of the antigen.

发育过程中的大多数程序性细胞死亡被认为是伴随DNA碎片的细胞凋亡。我们已经精确检查了生发中心的胸腺细胞死亡和B细胞死亡，即原位“细胞死亡”，发现它们是具有较重的核凝结而没有DNA碎片的肿瘤。它们与典型的凋亡完全不同，该凋亡的特征是DNA片段化和边缘染色质缩合。我们在体内重新评估了各种细胞死亡，并基于新的观点对原位细胞死亡进行了校正，以分析新型细胞死亡的机制，pyknosis的机制，并描述其生物学意义，并描述其生物学意义。我们分析了病因在生物中的形态中，尤其是在生物中，尤其是在此类中，尤其是在此类中的生物，以使其在生物中进行了研究，以使其在静止状态中，并在该病例中进行了研究。没有伴随DNA碎片，因此，我们得出的结论是它们不是凋亡。已经发现了由抗CD3抗体治疗触发的巨大细胞死亡，因为可以观察到形态学变化时它们在更早的阶段将DNA碎片。我们承担了一个项目来开发一个单克隆抗体，以检测pyknosis的最早伴有抑制性胸膜表面抗抑制性胸腺细胞的表面抗体，从而识别伴有含量均为莫克蛋白的表面抗体。该项目一直在进行中，并将进行直到抗原的开发。