Immunohistochemical analyses of the kinetics and distribution of macrophages, hepatic stellate cells and bile duct epithelia in the developing rat liver

Abstract

Non-parenchymal cells in the liver consist mainly of Kupffer cells, hepatic stellate (HS) cells and cholangiocytes. To establish base-line data and clarify the nature, this study investigated immunohistochemically the kinetics of these cell populations in developing liver of F344 rats. Samples were collected from fetuses on days 18 and 20, neonates on days 1, 4, 8, 15, and 21, and adults at weeks 5–35. ED1 (CD68)-positive macrophages showed highest number as early as fetal day 18, and then decreased gradually until adulthood. The numbers of macrophages reacting to ED2 (CD163), OX6 (MHC II), and SRA-E5 (scavenger receptor A, CD204) increased after birth (early neonates), and ED2- and SRA-E5-positive cell numbers were maintained until adulthood, but OX6-positive cell number decreased at late stages of neonates and adulthood. ED2- and SRA-E5-positive cells appeared along sinusoids, indicating Kupffer cells, whereas OX6-positive cells were limited in Glisson's sheath. Vimentin-positive HS cells were seen consistently from fetuses to adulthood. Desmin- and glial fibrillary acidic protein (GFAP)-positive HS cells tended to be seen in fetuses and early stages of neonates. HS cells reacting to α-smooth muscle actin (α-SMA) were not detectable. Cholangiocytes, reacting to cytokeratin 19 and AE1/AE3, began to be seen on fetus day 18 with faint reaction, and interlobular bile ducts were completed in Glisson's sheath by neonatal day 8. This study shows that there are heterogeneous macrophage populations and that HS cells can show various cytoskeletal proteins in rat hepatogenesis.