CHOLESTERYL ESTERS FROM OXIDIZED LOW-DENSITY LIPOPROTEINS ARE IN-VIVORAPIDLY HYDROLYZED IN RAT KUPFFER CELLS AND TRANSPORTED TO LIVER PARENCHYMAL-CELLS AND BILE
Mn. Pieters et al., CHOLESTERYL ESTERS FROM OXIDIZED LOW-DENSITY LIPOPROTEINS ARE IN-VIVORAPIDLY HYDROLYZED IN RAT KUPFFER CELLS AND TRANSPORTED TO LIVER PARENCHYMAL-CELLS AND BILE, Hepatology, 19(6), 1994, pp. 1459-1467
Human low-density lipoprotein was labeled in its cholesteryl ester moi
ety with [H-3]cholesteryl oleate or [H-3]cholesteryl oleoyl ether and
oxidized by exposure to 10 mu mol/L of cupric sulfate. The in vivo met
abolism of cholesteryl esters of oxidized low-density lipoprotein was
determined after injection into rats. When oxidized low density lipopr
otein was labeled with [H-3]cholesteryl oleoyl ether, a nonhydrolyzabI
e analog of cholesteryl oleate, Kupffer cells contributed to 55.1% +/-
4.1% of the total liver uptake 10 min after injection. When [H-3]chol
esteryl oleate-labeled oxidized low-density lipoprotein was injected,
the radiolabeled cholesterol esters were nearly completely hydrolyzed
within 1 hr of injection. Within this time, the Kupffer cell-associate
d radioactivity declined to 32% of the maximal uptake value. In serum,
the highest specific resecreted [H-3]cholesteryl (esters) were associ
ated with the serum high-density lipoprotein fraction, suggesting a ro
le for high-density lipoprotein as an in vivo cholesterol acceptor. Th
e kinetics of biliary secretion were studied in rats equipped with cat
heters in the bile duct, duodenum and heart. One hour after injection
of [H-3]cholesteryl oleate-labeled oxidized low-density lipoprotein, 4
.15% +/- 0.67% of the injected dose was secreted in the bile, mainly a
s bile acids. Six hours after injection, this value was 19.2% +/- 1.2%
. These values are three times higher than those for injected [H-3]cho
lesteryl oleate-labeled acetylated low-density lipoprotein, which is i
nitially mainly taken up by liver endothelial cells. The rapid process
ing of cholesteryl esters derived from oxidized low-density lipoprotei
n to bile acids indicates that Kupffer cells form an efficient protect
ion system against the atherogenic action of oxidized low-density lipo
protein in the blood compartment.