出版社：American Society for Biochemistry and Molecular Biology
摘要：The ability of apolipoprotein E (apoE) to be spared degradationin lysosomes and to recycle to the cell surface has been demonstratedby our group and others, but its physiologic relevance is unknown.In this study, we characterized apoE recycling in primary murinemacrophages and probed the effects of HDL and apoA-I on thisprocess. In cells pulsed with 125I·apoE bound to VLDL,intact apoE was found in the chase medium for up to 24 h afterthe pulse. Approximately 27 ± 5% of the apoE internalizedduring the pulse was recycled after 4 h of chase. Addition ofapoA-I and HDL increased apoE recycling to 45 ± 3% and46 ± 3%, respectively, similar to the amount of apoErecycled after pulsing the cells with 125I·apoE·HDL.In addition, apoA-I-producing macrophages from transgenic miceshowed increased apoE recycling at 4 h (38 ± 3%). IncreasedABCA1 expression potentiated apoE recycling, suggesting thatrecycling occurs via ABCA1. Finally, in the presence of apoA-I,recycled apoE exited the cells on HDL-like particles.
These results suggest that apoE recycling in macrophages maybe part of a larger signaling loop activated by HDL and directedat maximizing cholesterol losses from the cell.Supplementary key words cholesterol • efflux • atherosclerosis • high density lipoprotein • apolipoprotein E • macrophage
