Johan K. Kruijt

Characterization of the interaction of acetylated LDL and oxidatively modified LDL with human liver parenchymal and Kupffer cells in culture.

The interaction of acetylated low density lipoprotein (Ac-LDL) and oxidatively modified low density lipoprotein (Ox-LDL) with cultured human liver parenchymal cells and human Kupffer cells was investigated to define, for humans, the presence of scavenger receptors in the liver. A direct comparison of the capacity of Kupffer and parenchymal cells to interact with Ac-LDL and Ox-LDL indicated that the capacity of Kupffer cells per milligram of cell protein to degrade Ac-LDL and Ox-LDL is 14-fold and sixfold higher, respectively, than that of parenchymal cells. The degradation of both Ac-LDL and Ox-LDL by parenchymal cells and Kupffer cells could be inhibited by chloroquine and ammonium chloride, indicating that degradation occurs in the lysosomes. Competition studies showed that unlabeled Ox-LDL competed efficiently with the cell association and degradation of 125I-labeled Ac-LDL by human parenchymal cells and human Kupffer cells. However, unlabeled Ac-LDL did not compete (parenchymal cells) or only partially competed (40% in Kupffer cells) with the cell association and degradation of 125I-labeled Ox-LDL. Polyinosinic acid completely blocked the cell association and degradation of Ac-LDL and Ox-LDL with Kupffer cells while no significant effect on parenchymal cells was noted. It is concluded that human liver parenchymal cells contain a scavenger receptor that interacts with Ac-LDL and Ox-LDL and an additional recognition site that recognizes Ox-LDL specifically.(ABSTRACT TRUNCATED AT 250 WORDS)