Quantitative role of parenchymal and non-parenchymal liver cells in the uptake of [14C]sucrose-labelled low-density lipoprotein in vivo

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Abstract
In order to assess the relative importance of the receptor for low density lipoprotein (LDL) (apo-B,E receptor) in the various liver [rats] cell types for the catabolism of lipoproteins in vivo, human LDL was labeled with [14C]sucrose. Up to 4.5 h after i.v. injection, [14C]sucrose becomes associated with liver almost linearly with time. During this time the liver is responsible for 70-80% of the removal of LDL from blood. A comparison of the uptake of [14C]sucrose-labeled LDL and reductive-methylated [14C]sucrose-labeled LDL ([14C]sucrose-labeled Me-LDL) by the liver shows that methylation leads to a 65% decrease in the LDL uptake. This indicated that 65% of the LDL uptake by liver is mediated by a specific apo-B,E receptor. Parenchymal and non-prenchymal liver cells was isolated at various times after i.v. injection of [14C]sucrose-labeled LDL and [14C]sucrose-labeled Me-LDL. Non-parenchymal liver cells accumulate at least 60 times as much [14C]sucrose-labeled LDL than do parenchymnal cells when expressed per mg of cell protein. This factor is independent of the time after injection of LDL. Taking into account the relative protein contribution of the various liver cell types to the total liver, non-parenchymal cells are responsible for 71% of the total liver uptake of [14C]sucrose-labeled LDL. A comparison of the cellular uptake of [14C]sucrose-labeled LDL and [14C]sucrose-labeled Me-LDL after 4.5 h circulation indicates that 79% of the uptake of LDL by non-parenchymal cells is receptor-dependent. With parenchymal cells no significant difference in uptake between [14C]sucrose-labeled LDL and [14C]sucrose-labeled Me-LDL was found. A further separation of the non-parenchymal cells into Kupffer and endothelial cells by centrifugal elutriation shows that within the non-parenchymal cell preparation solely by Kupffer cells are responsible for the receptor-dependent uptake of LDL. In rats the Kupffer cell is the main cell type responsible for the receptor-dependent catabolism of liproproteins containing only apolipoprotein B.

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