title: Relative contributions of ABCA1 and SR-BI to cholesterol efflux to serum from fibroblasts and macrophages.
abstract: OBJECTIVE
  Cholesterol efflux is achieved by several mechanisms. This study examines contributions of these pathways to efflux to human serum.
  
  
  RESULTS
  Human fibroblasts were stably transfected with SR-BI while ABCA1 was upregulated. Quantitation of cholesterol efflux to human serum demonstrated that there was efflux from cells without either protein. Expression of ABCA1 produced a small increase in efflux, whereas SR-BI expression had a dramatic impact. To quantitate ABCA1 and SR-BI contribution, fibroblasts were pretreated with Probucol and BLT-1 to, respectively, inhibit these efflux proteins. Exposing SR-BI-expressing fibroblasts to BLT-1 inhibited efflux by 67%. Probucol pretreatment of ABCA1-expressing fibroblasts reduced efflux to serum by 26%. A large fraction of total efflux was uninhibited. For both J774 and mouse peritoneal macrophages, contributions of either ABCA1 or SR-BI to efflux to serum were low, with background/uninhibited efflux contributing from 70% to 90% of total efflux.
  
  
  CONCLUSIONS
  We have shown that ABCA1-mediated efflux to serum responds to the pool of lipid-free/poor apolipoproteins, whereas phospholipid-containing particles mediate SR-BI efflux. Although SR-BI and ABCA1 contribute to efflux from fibroblasts and cholesterol-enriched macrophages, a large proportion of the total efflux to human serum is mediated by a mechanism that is neither SR-BI nor ABCA1.
authors.affiliation: GI and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: MyNgan
authors.initials: M
authors.lastname: Duong
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Collins
authors.forename: Weijun
authors.initials: W
authors.lastname: Jin
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zanotti
authors.forename: Elda
authors.initials: E
authors.lastname: Favari
authors.forename: George H
authors.initials: GH
authors.lastname: Rothblat
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001798:Blood Proteins / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002461:Cell Line, Transformed; D008076:Cholesterol, HDL / Q000493:pharmacokinetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D013882:Thiosemicarbazones / Q000494:pharmacology; D014162:Transfection
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001798:Blood Proteins; D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D013882:Thiosemicarbazones; D011341:Probucol