Effects of particle size on cell uptake of model triglyceride-rich particles with and without apoprotein E.
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.
Granot
E
E
Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Schwiegelshohn
B
B
Tabas
I
I
Gorecki
M
M
Vogel
T
T
Carpentier
Y A
YA
Deckelbaum
R J
RJ
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
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D004655:Emulsions; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides