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Liver cell rearrangement and apoptosis duirng retardation of fetal hematopoiesis

胎儿造血迟缓期间的肝细胞重排和凋亡

基本信息

批准号：
14570031
负责人：
SASAKI Kazunobu
金额：
$ 1.98万
依托单位：
KAWASAKI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570031/
关键词：
Liver Hematopoiesis Hepatocyte Programmed cell death Macrophages Apoptosis F4 80 Iron staining Neonatal mouse 細胞死マウス肝芽細胞新生子肝臓超微形態 TUNEL

项目摘要

Neonatal livers examined by the TUNEL method have been found to contain dying hematopoietic cells, and a few hepatocytes have been also found to be positive. Regarding the ultrastructural features of dying hepatocytes, two different types of cell death; types I and II were observed. The early features of type I cell death appeared in the cytoplasm, which was characterized by dilated rough endoplasmic reticulum. Type II cell death was characterized by compaction and margination of heterochromatin resulting in the formation of sharply circumscribed masses. Type I corresponds to cytoplasmic type degeneration and non-apoptotic death, whereas type II corresponds to nuclear type cell death or classical apoptotic death. The incidence of type I cell death was much higher than that of type II.Immunochistochemical staining with rat anti-mouse macrophage monoclonal antibody F4/80 permits a more objective identification of macrophages under light micorscopy. There was a rapid increase in the number of F4/80-positive cells per unit area from 11 days of gestation, but there was a significant decrease between 4 and 13 days after birth(p<0.01). In fetal livers, F4/80-positive cells were identified among hepatic cell cords as central macrophages of erythroblastic islands in the hematopoietic foci. The macrophages contained phagosomes from extruded nuclei of erythroblasts and Fe-positive inclusions. At 19 days of gestation, a few F4/80-positive cells without hematopoietic cells also appeared among hepatocytes. In neonatal livers, a few small F4/80-positive but Fe-negative mononuclear cells also appeared. Some of large macrophages underwent cell death not only through classical apoptosis but also through a process called "dark cell formation." The small F4/80-positive but Fe-negative mononuclear cells in early postnatal livers could be considered as a candidate for a precursor of hepatic resident macrophages.

用TUNEL法检查的新生儿肝脏中发现含有垂死的造血细胞，少数肝细胞也呈阳性。关于死亡肝细胞的超微结构特征，观察到两种不同类型的细胞死亡; I型和II型。I型细胞死亡的早期特征出现在细胞质中，以粗面内质网扩张为特征。II型细胞死亡的特征在于异染色质的压实和边集，导致形成明显的限制性肿块。I型对应于细胞质型变性和非凋亡性死亡，而II型对应于核型细胞死亡或经典凋亡性死亡。I型细胞死亡的发生率远高于II型。免疫组化染色与大鼠抗小鼠巨噬细胞单克隆抗体F4/80允许更客观的鉴定巨噬细胞在光镜下。单位面积F4/80阳性细胞数从孕11天开始迅速增加，但在生后4 ~ 13天明显减少（p<0.01）。在胎肝中，F4/80阳性细胞在肝细胞索中被鉴定为造血灶中成红细胞岛的中央巨噬细胞。巨噬细胞含有吞噬体从挤出的核的成红细胞和铁阳性夹杂物。在妊娠19天，肝细胞中也出现了少量F4/80阳性细胞，但没有造血细胞。在新生儿肝脏中，也出现了一些F4/80阳性但Fe阴性的小单核细胞。一些大的巨噬细胞不仅通过经典的凋亡，而且通过一个称为“暗细胞形成”的过程进行细胞死亡。“出生后早期肝脏中F4/80阳性但Fe阴性的小单核细胞可以被认为是肝脏驻留巨噬细胞的前体的候选者。