title: Cellular differences in lipoprotein lipase-mediated uptake of low density lipoproteins.
abstract: Lipoprotein lipase (LPL) increases the cellular uptake and degradation of LDL by fibroblasts and macrophages via a heparin-sensitive process. The roles of the LDL receptor, LDL receptor-related protein (LRP), and proteoglycans in this process were studied. In up-regulated human fibroblasts, LPL increased degradation of 125I-low density lipoprotein (LDL) (5 micrograms/ml) only 30% during a 6-h incubation at 37 degrees C. Monoclonal antibody 47 (which interacts with the receptor binding region of apoB) decreased LDL degradation 93% in the absence of LPL, but did not reduce the LPL-mediated increase in degradation. In contrast, addition of the 39-kDa receptor-associated protein (RAP) caused a 43% decrease in the LPL-dependent LDL degradation in non-up-regulated fibroblasts. Monoclonal antibody 47 did not decrease LDL degradation by THP-1 macrophages and RAP caused a < 13% decrease in LPL-mediated LDL degradation. LPL also increased the association of acetyl LDL with the surface of the macrophages but did not increase acetyl LDL degradation. The kinetics of LPL-mediated LDL metabolism in macrophages was then compared with that in fibroblasts. The half-lives of cell surface LDL and LPL during a subsequent 37 degrees C incubation were approximately 1 h in THP-1 cells versus 6 h in fibroblasts. In addition, 50% of the 125I-LDL and 30% of the 125I-LPL were degraded within 3 h. After metabolic labeling of THP-1 proteoglycans with 35SO4, > 30% of pericellular heparan sulfate was lost between 2-4 h of the chase period. Therefore, some of the LPL-mediated LDL degradation in the THP-1 cells could be accounted for by internalization of cell surface proteoglycans. We conclude that LRP, but not the LDL receptor, is involved in LPL-mediated degradation of LDL in fibroblasts. This process is much more rapid in THP-1 cells and in addition to LRP may involve other receptors and internalization of proteoglycans.
authors.affiliation: Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032.
authors.forename: J C
authors.initials: JC
authors.lastname: Obunike
authors.forename: I J
authors.initials: IJ
authors.lastname: Edwards
authors.forename: S C
authors.initials: SC
authors.lastname: Rumsey
authors.forename: L K
authors.initials: LK
authors.lastname: Curtiss
authors.forename: W D
authors.initials: WD
authors.lastname: Wagner
authors.forename: R J
authors.initials: RJ
authors.lastname: Deckelbaum
authors.forename: I J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000107:Acetylation; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D011973:Receptors, LDL / Q000502:physiology; D015854:Up-Regulation
chemical_list: D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008071:Lipoprotein Lipase; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D011973:Receptors, LDL