title: Effects of particle size on cell uptake of model triglyceride-rich particles with and without apoprotein E.
abstract: The effect of apoprotein E on cellular uptake of "VLDL-size" and "IDL-size" triacylglycerol-phospholipid emulsion particles was studied in J-774 macrophages and fibroblasts. In the absence of apoprotein E (apo E), uptake of the smaller IDL-size particles was up to 2-fold higher by mass and 100-fold higher as calculated by particle number. Apo E enhanced the uptake of both VLDL-size and IDL-size emulsion particles, but the effect was greater on the uptake of larger particles (4-5-fold) as compared to up to a 2-fold increase in the uptake of IDL-size particles. In fibroblasts, particle uptake was less than in macrophages (30-50%), but preferential uptake of smaller particles was similarly observed. Particle internalization was demonstrated by 125I-apo E degradation and resistance to particle release by heparin-suramin. In the absence of apo E, cholesteryl ester of emulsion particles (prepared with trace amounts of [3H]cholesteryl ester) was hydrolyzed to free cholesterol, proving internalization and intracellular metabolism. Double-label experiments using DiI-labeled emulsion particles, in the absence and presence of apo E, showed that emulsion particles are rapidly targeted to perinuclear lysosomes. Thus, at physiological concentrations of triglyceride-rich particles, non-receptor-mediated uptake is a mechanism for the uptake of VLDL-size and IDL-size particles into cells.
authors.affiliation: Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
authors.forename: E
authors.initials: E
authors.lastname: Granot
authors.forename: B
authors.initials: B
authors.lastname: Schwiegelshohn
authors.forename: I
authors.initials: I
authors.lastname: Tabas
authors.forename: M
authors.initials: M
authors.lastname: Gorecki
authors.forename: T
authors.initials: T
authors.lastname: Vogel
authors.forename: Y A
authors.initials: YA
authors.lastname: Carpentier
authors.forename: R J
authors.initials: RJ
authors.lastname: Deckelbaum
mesh_terms: D001057:Apolipoproteins E / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D004655:Emulsions; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D008113:Liver Neoplasms / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010316:Particle Size; D014280:Triglycerides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D001057:Apolipoproteins E; D002788:Cholesterol Esters; D004655:Emulsions; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides