Mechanisms of pyknotic cell death in vivo and their biological significance

在发育过程中，大多数程序性细胞死亡被认为是伴随DNA片段化的细胞凋亡。我们已经精确地检查了胸腺细胞死亡和B细胞死亡在生发中心，即，结果发现，它们是核固缩，核浓缩，没有DNA断裂;它们完全不同于典型的凋亡，其特征是DNA断裂和边缘染色质浓缩。我们重新评估了各种体内细胞死亡，并根据新的观点对原位细胞死亡进行了重新分类，以分析新的细胞死亡类型--固缩的机制，并阐明其生物学意义。我们从形态学上分析了发育过程中体内细胞死亡，特别是在趾间组织中观察到的细胞死亡，并发现该组织中的细胞死亡不伴随DNA片段化，因此，我们得出结论，它们不是凋亡。抗CD 3抗体治疗引发的大量细胞死亡已被发现是典型的细胞凋亡，因为它们在可以观察到形态学变化的早期阶段使DNA片段化。我们已经开展了一个项目，开发一种单克隆抗体来检测核固缩的最早迹象，核固缩是死亡胸腺细胞的表面抗原，被巨噬细胞识别并摄取。该项目一直在进行中，并将继续进行，直到开发出抗原。

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.