Uptake and degradation of human low-density lipoprotein by human liver parenchymal and Kupffer cells in culture.
The association with and degradation by cultured human parenchymal liver cells and human Kupffer cells of human low-density lipoprotein (LDL) was investigated in order to define, for the human situation, the relative abilities of the various liver cell types to interact with LDL. With both human parenchymal liver cells and Kupffer cells the association of LDL with the cells followed saturation kinetics which were coupled to LDL degradation. The association of LDL (per mg of cell protein) to both cell types was comparable, but the association with human Kupffer cells was much more efficiently coupled to degradation than was the case in parenchymal cells. The capacity of human Kupffer cells to degrade LDL was consequently 18-fold higher (per mg of cell protein) than that of the human parenchymal liver cells. Competition studies showed that unlabelled LDL competed efficiently with the cell association and degradation of 125I-labelled LDL with both parenchymal and Kupffer cells, while unlabelled acetyl-LDL was ineffective. The degradation of LDL by parenchymal and Kupffer cells was blocked by chloroquine and NH4Cl, indicating that it occurs in the lysosomes. Binding and degradation of LDL by human liver parenchymal cells and human Kupffer cells appeared to be completely calcium-dependent. It is concluded that the association and degradation of LDL by human Kupffer and parenchymal liver cells proceeds through the specific LDL receptor, whereas the association of LDL to Kupffer cells is more efficiently coupled to degradation. The presence of the highly active LDL receptor on human Kupffer cells might contribute significantly to LDL catabolism by human liver, especially under conditions whereby the LDL receptor on parenchymal cells is down-regulated.
Kamps
J A
JA
Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
Kruijt
J K
JK
Kuiper
J
J
Van Berkel
T J
TJ
D000643:Ammonium Chloride / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology
D008077:Lipoproteins, LDL; D000643:Ammonium Chloride; D002738:Chloroquine; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium