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.