Liver cell rearrangement and apoptosis duirng retardation of fetal hematopoiesis

经TUNEL法检查的新生儿肝脏中含有正在死亡的造血细胞，少数肝细胞也呈阳性。关于垂死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，其特征是粗面内质网扩张。II型细胞死亡的特征是异染色质致密和边集，导致明显的边界肿块的形成。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的凋亡性死亡。用大鼠抗小鼠巨噬细胞单抗F4/80进行免疫组织化学染色，可以在光镜下更客观地鉴定巨噬细胞。单位面积的F4/80阳性细胞数从妊娠11d开始迅速增加，但在出生后4~13d显著减少(p&lt；0.01)。在胎肝中，F4/80阳性细胞位于肝细胞带之间，是造血灶中红系细胞岛的中央巨噬细胞。巨噬细胞含有红细胞胞核膨出的吞噬小体和铁阳性包涵体。妊娠19天时，肝细胞中也可见少量F4/80阳性细胞，但无造血细胞。在新生儿肝脏中，也可见少量F4/80阳性而铁阴性的单个核细胞。一些大的巨噬细胞不仅经历了经典的细胞死亡，还经历了一个被称为“暗细胞形成”的过程。出生后早期肝脏中F4/80阳性而铁阴性的小单个核细胞可作为肝内滞留巨噬细胞的前体细胞。

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.