Sainio-Pöllänen S, Erkkilä S, Alanko S, Hänninen A, Pöllänen P, Simell O
Department of Anatomy, University of Turku, Finland.
Pancreas. 1998 Mar;16(2):154-9. doi: 10.1097/00006676-199803000-00008.
The role of Fas ligand-induced lymphocyte apoptosis in the development of insulitis was studied in nonobese diabetic (NOD) mice. Fas ligand with a molecular weight of 45 kD appeared in the pancreas of NOD mice during the onset of insulitis as demonstrated by western blot analysis. In situ DNA end-labeling (ISEL) of the pancreases of NOD mice demonstrated positive cells in the islets of Langerhans, with an age-dependent increase in the density and frequency of animals with islets containing ISEL-positive cells. In the pancreatic islets of BALB/c mice, no ISEL-positive cells were observed in any of the age groups studied. In ultrastructural analysis degenerating cells with condensed or fragmented nuclei and plasma membranes detached from neighboring cells were observed both in and around the islets. In some cases, these cells were being phagocytosed by the neighboring islet cells. Degenerating cells with characteristics of lymphocytes were seen in contact with healthy lymphocytes around the islets. Neutralizing Fas ligand antibodies affected 3H-thymidine incorporation of CD3+CD28+ pancreatic lymphocytes from 12- to 30-week-old NOD mice in one of three cultures. There was no difference in the effect of neutralizing Fas ligand antibodies between pancreatic and blood lymphocytes. The present results on an increase in density of apoptotic cells in pancreatic islets of NOD mice simultaneously with the onset of insulitis and appearance of Fas ligand suggest that the pancreas infiltrating lymphocytes may be destroyed by Fas ligand-induced apoptosis.
在非肥胖型糖尿病（NOD）小鼠中研究了Fas配体诱导的淋巴细胞凋亡在胰岛炎发生发展中的作用。通过蛋白质印迹分析表明，分子量为45 kD的Fas配体在胰岛炎发作期间出现在NOD小鼠的胰腺中。对NOD小鼠胰腺进行原位DNA末端标记（ISEL）显示，胰岛中有阳性细胞，并且含有ISEL阳性细胞的胰岛的动物密度和频率随年龄增加。在BALB/c小鼠的胰岛中，在所研究的任何年龄组中均未观察到ISEL阳性细胞。在超微结构分析中，在胰岛内和周围均观察到细胞核浓缩或破碎、质膜与相邻细胞分离的退化细胞。在某些情况下，这些细胞被相邻的胰岛细胞吞噬。在胰岛周围可见具有淋巴细胞特征的退化细胞与健康淋巴细胞接触。在三种培养物中的一种中，中和Fas配体抗体影响了12至30周龄NOD小鼠CD3 + CD28 +胰腺淋巴细胞的3H-胸腺嘧啶核苷掺入。胰腺淋巴细胞和血液淋巴细胞在中和Fas配体抗体的作用上没有差异。目前关于NOD小鼠胰岛中凋亡细胞密度增加与胰岛炎发作和Fas配体出现同时发生的结果表明，浸润胰腺的淋巴细胞可能被Fas配体诱导的凋亡所破坏。
