Lipoprotein lipase-dependent binding and uptake of low density lipoproteins by THP-1 monocytes and macrophages: possible involvement of lipid rafts.
Lipoprotein lipase (LPL) is produced by cells in the artery wall and can mediate binding of lipoproteins to cell surface heparan sulfate proteoglycans (HSPG), resulting in endocytosis (the bridging function). Active, dimeric LPL may dissociate to inactive monomers, the main form found in plasma. We have studied binding/internalization of human low density lipoprotein (LDL), mediated by bovine LPL, using THP-1 monocytes and macrophages. Uptake of (125)I-LDL was similar in monocytes and macrophages and was not affected by the LDL-receptor family antagonist receptor-associated protein (RAP) or by the phagocytosis inhibitor cytochalasin D. In contrast, uptake depended on HSPG and on membrane cholesterol. Incubation in the presence of dexamethasone increased the endogenous production of LPL by the cells and also increased LPL-mediated binding of LDL to the cell surfaces. Monomeric LPL was bound to the cells mostly in a heparin-resistant fashion. We conclude that the uptake of LDL mediated by LPL dimers is receptor-independent and involves cholesterol-enriched membrane areas (lipid rafts). Dimeric and monomeric LPL differ in their ability to mediate binding/uptake of LDL, probably due to different mechanisms for binding/internalization.
Makoveichuk
Elena
E
Department of Medical Biosciences, Physiological Chemistry, Bldg 6M, 3rd floor, Umeå University, SE-901 87 Umeå, Sweden.
Castel
Susanna
S
Vilaró
Senen
S
Olivecrona
Gunilla
G
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000502:physiology; D015638:Cytochalasin D / Q000494:pharmacology; D019281:Dimerization; D019763:Heparin Lyase / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding
D026563:LDL-Receptor Related Protein-Associated Protein; D008077:Lipoproteins, LDL; D015638:Cytochalasin D; D002784:Cholesterol; D008071:Lipoprotein Lipase; D019763:Heparin Lyase