Uptake and metabolism of high-density lipoproteins by cultured rabbit hepatocytes.

The selective uptake and internalization of core components of high-density lipoproteins (HDL) were examined in primary monolayer cultures of rabbit hepatocytes. Using [14C]sucrose as a surface marker covalently attached to apolipoprotein and [3H]cholesteryl linoleyl ether as a core marker, there was a 5-6-fold greater internalization of cholesteryl ether than sucrose-labeled apolipoprotein during 48 h of culture. The rate of uptake of [3H]cholesteryl linoleyl ether was 263 +/- 29 ng apo HDL/mg cell protein per h during the initial 8 h of culture, but averaged 101 +/- 32 ng apo HDL/mg cell protein per h over the 48 h culture period. Concomitant with this apparent selective uptake of cholesteryl ester core, there was a change in the HDL size distribution, with the appearance of a distinct population of smaller 4.3 nm radius particles in addition to the originally predominant particles of 4.9 nm radius. This was associated with a significant reduction of cholesteryl ester as a percentage of lipoprotein mass from 15.5 +/- 1.2 to 11.0 +/- 1.2 (P less than 0.001) and a reduction in cholesteryl ester:protein mass ratio from 0.30 +/- 0.01 to 0.19 +/- 0.01 (P less than 0.001). There was no change in the mass ratio of HDL triacylglycerol to protein. Thus rabbit hepatocytes in culture exhibit the capacity to selectively extract cholesteryl ester from HDL and produce smaller HDL particles.