Hepatic lipase (HL) is thought to be located at the vascular endotheli
um in the liver. However, it has also been implicated in the binding a
nd internalization of chylomicron remnants in the parenchymal cells. I
n view of this apparent discrepancy between localization and function,
we re-investigated the localization of HL in rat liver using biochemi
cal and immunohistochemical techniques. The binding of HL to endotheli
al cells was studied in primary cultures of rat liver endothelial cell
s. Endothelial cells bound HL in a saturable manner with high affinity
. However, the binding capacity accounted for at most 1% of the total
HL activity present in the whole liver. These results contrasted with
earlier studies, in which non-parenchymal cell (NPC) preparations had
been found to bind HL with a high capacity. To study HL binding to the
different components of the NPC preparations, we separated endothelia
l cells, Kupffer cells and blebs by counterflow elutriation. Kupffer c
ells and endothelial cells showed a relatively low HL-binding capacity
. In contrast, the blebs, representing parenchymal-cell-derived materi
al, had a high HL-binding capacity (33 m-units/mg of protein) and acco
unted for more than 80% of the total HL binding in the NPC preparation
. In contrast with endothelial and Kupffer cells, the HL-binding capac
ity of parenchymal cells could account for almost all the HL activity
found in the whole liver. These data strongly suggest that HL binding
occurs at parenchymal liver cells. To confirm this conclusion in situ,
we studied HL localization by immunocytochemical techniques. Using im
munofluorescence, we confirmed the sinusoidal localization of HL. Immu
noelectron microscopy demonstrated that virtually all HL was located a
t the microvilli of parenchymal liver cells, with a minor amount at th
e endothelium. We conclude that, in rat liver, HL is localized at the
microvilli of parenchymal cells.