K. Rijhsinghani et al., IMMUNOELECTRON MICROSCOPY IDENTIFICATION OF EARLY PROLIFERATING CELLSIN RAT-LIVER TISSUE DURING HYPERPLASIA INDUCED BY LEAD NITRATE, Hepatology, 17(4), 1993, pp. 685-692
Recent studies have suggested that hepatic stem cells may be involved
in at least some forms of liver epithelial growth. To obtain further i
nformation on this controversial hypothesis, we treated rats with lead
nitrate to induce liver growth and identified the cells undergoing ea
rly DNA synthesis by bromodeoxyuridine immunohistochemistry, using bot
h light and electron microscopic detection methods. Eight hours after
an intravenous injection of lead nitrate 100 mumol/kg, DNA synthesis w
as detected in a few scattered hepatocytes and in nonparenchymal cells
in portal connective tissue. At the light microscopic level, identifi
cation of nonparenchymal cells was limited to bile duct epithelial cel
ls. Other cell types were also labeled, but their identity could not b
e established. At the ultrastructural level, however, four types of no
nparenchymal cells were identified as containing bromodeoxyuridine imm
unogold particles. These four types included bile duct epithelial cell
s, fibroblasts, macrophages and nondescript periductular cells. These
periductular cells displayed certain ultrastructural features of bile
duct cells but did not line a lumen or display microvilli on their api
cal membrane, nor did they reside within the bile duct basement membra
ne. Because proliferation of nonparenchymal cells in portal areas prec
eded that of hepatocytes, it is suggested that the former reaction ref
lects a direct mitogenic effect of lead nitrate and not an adaptive gr
owth response secondary to parenchymal enlargement. However, whether D
NA synthesis in periductular cells or bile duct cells reflects activat
ion of hepatic stem cells cannot be established from the present morph
ological observations. If so, such a progenitor compartment must be do
rmant because it does not seem to play a functional role in this and o
ther forms of adult liver epithelial growth.