Importance of macrophage cholesterol content on the flux of cholesterol mass

Net flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-...

Full description

Bibliographic Details
Main Authors: Sandhya Sankaranarayanan, Margarita de la Llera-Moya, Denise Drazul-Schrader, Bela F. Asztalos, Ginny L. Weibel, George H. Rothblat
Format: Article
Language:English
Published: Elsevier 2010-11-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520409575
_version_ 1818740442804518912
author Sandhya Sankaranarayanan
Margarita de la Llera-Moya
Denise Drazul-Schrader
Bela F. Asztalos
Ginny L. Weibel
George H. Rothblat
author_facet Sandhya Sankaranarayanan
Margarita de la Llera-Moya
Denise Drazul-Schrader
Bela F. Asztalos
Ginny L. Weibel
George H. Rothblat
author_sort Sandhya Sankaranarayanan
collection DOAJ
description Net flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-normal and -enriched J774 and elicited mouse peritoneal macrophage cells. Net cell-cholesterol effluxes were observed when cholesterol-enriched J774 cells were incubated with 3.5% apolipoprotein (apo) B depleted human serum, HDL3, and apo A-I. Net cell-cholesterol influxes were observed when cholesterol-normal J774 cells were incubated with the same acceptors except apo A-I. When incubated with 2.5% individual sera, cholesterol mass efflux in free cholesterol (FC)-enriched J774 cells correlated with the HDL-cholesterol (HDL-C) concentrations (r2= 0.4; P=0.003), whereas cholesterol mass influx in cholesterol-normal J774 cells correlated with the LDL cholesterol (LDL-C) concentrations (r2= 0.6; P<0.0001) of the individual sera. A positive correlation was observed between measurements of [3H]cholesterol efflux and reductions in cholesterol mass (r2= 0.4; P=0.001) in FC-enriched J774 cells. In conclusion, isotopic efflux measurements from cholesterol-normal or cholesterol-enriched cells provide an accurate measurement of relative ability of an acceptor to remove labeled cholesterol under a specific set of experimental conditions, i.e., efflux potential. Moreover, isotopic efflux measurements can reflect changes in cellular cholesterol mass if the donor cells are enriched with cholesterol.
first_indexed 2024-12-18T01:40:48Z
format Article
id doaj.art-fcea3e9d3a4049389bd75ab70ea4cc38
institution Directory Open Access Journal
issn 0022-2275
language English
last_indexed 2024-12-18T01:40:48Z
publishDate 2010-11-01
publisher Elsevier
record_format Article
series Journal of Lipid Research
spelling doaj.art-fcea3e9d3a4049389bd75ab70ea4cc382022-12-21T21:25:21ZengElsevierJournal of Lipid Research0022-22752010-11-01511132433249Importance of macrophage cholesterol content on the flux of cholesterol massSandhya Sankaranarayanan0Margarita de la Llera-Moya1Denise Drazul-Schrader2Bela F. Asztalos3Ginny L. Weibel4George H. Rothblat5Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PADivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PADivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PALipid Metabolism Laboratory, Tufts University, Boston, MADivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PATo whom correspondence should be addressed. rothblat@email.chop.edu; Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PANet flux of cholesterol represents the difference between efflux and influx and can result in net cell-cholesterol accumulation, net cell-cholesterol depletion, or no change in cellular cholesterol content. We measured radiolabeled cell-cholesterol efflux and cell-cholesterol mass using cholesterol-normal and -enriched J774 and elicited mouse peritoneal macrophage cells. Net cell-cholesterol effluxes were observed when cholesterol-enriched J774 cells were incubated with 3.5% apolipoprotein (apo) B depleted human serum, HDL3, and apo A-I. Net cell-cholesterol influxes were observed when cholesterol-normal J774 cells were incubated with the same acceptors except apo A-I. When incubated with 2.5% individual sera, cholesterol mass efflux in free cholesterol (FC)-enriched J774 cells correlated with the HDL-cholesterol (HDL-C) concentrations (r2= 0.4; P=0.003), whereas cholesterol mass influx in cholesterol-normal J774 cells correlated with the LDL cholesterol (LDL-C) concentrations (r2= 0.6; P<0.0001) of the individual sera. A positive correlation was observed between measurements of [3H]cholesterol efflux and reductions in cholesterol mass (r2= 0.4; P=0.001) in FC-enriched J774 cells. In conclusion, isotopic efflux measurements from cholesterol-normal or cholesterol-enriched cells provide an accurate measurement of relative ability of an acceptor to remove labeled cholesterol under a specific set of experimental conditions, i.e., efflux potential. Moreover, isotopic efflux measurements can reflect changes in cellular cholesterol mass if the donor cells are enriched with cholesterol.http://www.sciencedirect.com/science/article/pii/S0022227520409575cholesterol-enrichedeffluxinfluxreverse cholesterol transport
spellingShingle Sandhya Sankaranarayanan
Margarita de la Llera-Moya
Denise Drazul-Schrader
Bela F. Asztalos
Ginny L. Weibel
George H. Rothblat
Importance of macrophage cholesterol content on the flux of cholesterol mass
Journal of Lipid Research
cholesterol-enriched
efflux
influx
reverse cholesterol transport
title Importance of macrophage cholesterol content on the flux of cholesterol mass
title_full Importance of macrophage cholesterol content on the flux of cholesterol mass
title_fullStr Importance of macrophage cholesterol content on the flux of cholesterol mass
title_full_unstemmed Importance of macrophage cholesterol content on the flux of cholesterol mass
title_short Importance of macrophage cholesterol content on the flux of cholesterol mass
title_sort importance of macrophage cholesterol content on the flux of cholesterol mass
topic cholesterol-enriched
efflux
influx
reverse cholesterol transport
url http://www.sciencedirect.com/science/article/pii/S0022227520409575
work_keys_str_mv AT sandhyasankaranarayanan importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass
AT margaritadelalleramoya importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass
AT denisedrazulschrader importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass
AT belafasztalos importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass
AT ginnylweibel importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass
AT georgehrothblat importanceofmacrophagecholesterolcontentonthefluxofcholesterolmass