Submitted on October 20, 2004
Revised on March 28, 2005
Accepted on March 28, 2005
The recycling of apolipoprotein E in macrophages: Influence of HDL and apolipoprotein AI
Alyssa H. Hasty, Michelle R. Plummer, Karl H. Weisgraber, MacRae F. Linton, Sergio Fazio, and Larry L. Swift
Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0615
Corresponding Author: alyssa.hasty{at}vanderbilt.edu
The ability of apolipoprotein E (apoE) to be spared degradation in lysosomes and to recycle to the cell surface has clearly been shown by our group and by others. This phenomenon occurs in many different cell types, including fibroblasts, hepatocytes, and macrophages, but its physiologic relevance is yet to be defined. In this study, we sought to characterize the connections between HDL and recycling of apoE in primary murine macrophages. In pulse-chase studies, 125IapoE bound to VLDL was recycled and found intact in cells and in the chase media for up to 24 h. The amount of apoE recycled and secreted at 4 h after the pulse was 27±5% of the amount internalized. Similar experiments using 125IapoEHDL showed apoE recycling at 4 h was increased to 42±4% of the internalized apoE. Moreover, addition of apoAI and HDL increased apoE recycling to 45±3% and 46±3%, respectively. In addition, apoAI-producing macrophages from transgenic mice also showed increased apoE recycling at 4 h (38 ± 3%). It is possible that apoAI-accelerated apoE recycling occurs via ABC-AI, as increased ABC-AI expression also potentiated apoE recycling to 40±3%. Finally, in the presence of apoAI, the recycled apoE exited the cells on HDL-like particles. These results suggest that apoE recycling in macrophages may be part of a larger signaling loop activated by HDL and directed at maximizing cholesterol losses from the cell.
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