出版社：American Society for Biochemistry and Molecular Biology
摘要：Endocytosis of LDL and modified LDL represents regulated andunregulated cholesterol delivery to macrophages. To elucidatethe mechanisms of cellular cholesterol transport and egressunder both conditions, various primary macrophages were labeledand loaded with cholesterol or cholesteryl ester from LDL oracetylated low density lipoprotein (AcLDL), and the cellularcholesterol traffic pathways were examined. Confocal microscopyusing fluorescently labeled 3,3'-dioctyldecyloxacarbocyanineperchlorate-labeled LDL and 1,1'-dioctyldecyl-3,3,3',3'-tetramethylindodicarbocyanineperchlorate-labeled AcLDL demonstrated their discrete trafficpathways and accumulation in distinct endosomes. ABCA1-mediatedcholesterol efflux to apolipoprotein A-I (apoA-I) was much greaterfor AcLDL-loaded macrophages compared with LDL. Treatment withthe liver X receptor ligand 22-OH increased efflux to apoA-Iin AcLDL-loaded but not LDL-loaded cells. In contrast, at alevel equivalent to AcLDL, LDL-derived cholesterol was preferentiallyeffluxed to HDL, in keeping with increased ABCG1. In vivo studiesof reverse cholesterol transport (RCT) from cholesterol-labeledmacrophages injected intraperitoneally demonstrated that LDL-derivedcholesterol was more efficiently transported to the liver andsecreted into bile than AcLDL-derived cholesterol. This indicatesa greater efficiency of HDL than lipid-poor apoA-I in interstitialfluid in controlling in vivo RCT. These assays, taken together,emphasize the importance of mediators of diffusional cholesterolefflux in RCT.Supplementary key words cholesterol efflux • ATP binding cassette transporter A1 • ATP binding cassette transporter G1 • scavenger receptor class B type I • low density lipoprotein
