Recognition of chylomicron remnants and beta-migrating very-low-density lipoproteins by the remnant receptor of parenchymal liver cells is distinct from the liver alpha 2-macroglobulin-recognition site.
The uptake in vivo of chylomicrons and beta-migrating very-low-density lipoprotein (beta-VLDL) by rat liver, which is primarily carried out by parenchymal cells, is inhibited, 5 min after injection, to respectively 35 and 8% of the control values after preinjection of lactoferrin. The decrease in the uptake of lipoproteins by the liver caused by lactoferrin is a specific inhibition of uptake by parenchymal cells. Competition studies in vitro demonstrate that chylomicron remnants and beta-VLDL compete for the same recognition site on parenchymal cells. Data obtained in vivo together with the competition studies performed in vitro indicate that chylomicron remnants and beta-VLDL interact specifically with the same remnant receptor. Hepatic uptake of 125I-labelled-alpha 2-macroglobulin in vivo, mediated equally by parenchymal and endothelial cells, is not decreased by preinjection of lactoferrin and no effect on the parenchymal-cell-mediated uptake is found. In vitro, alpha 2-macroglobulin and chylomicron remnants or beta-VLDL show no cross-competition. Culturing of parenchymal cells for 24-48 h leads to a decrease in the cell association of alpha 2-macroglobulin to 26% of the initial value, while the cell association of beta-VLDL with the remnant receptor is not influenced. It is concluded that beta-VLDL and chylomicron remnants are recognized by a specific remnant receptor on parenchymal liver cells, while uptake of alpha 2-macroglobulin by liver is carried out by a specific receptor system (presumably involving the LDL-receptor-related protein) which shows properties that are distinct from those of the remnant receptor.
van Dijk
M C
MC
Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
Ziere
G J
GJ
Boers
W
W
Linthorst
C
C
Bijsterbosch
M K
MK
van Berkel
T J
TJ
D000818:Animals; D002478:Cells, Cultured; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D002914:Chylomicrons; D008079:Lipoproteins, VLDL; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D007781:Lactoferrin