Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 18 February 1983:
Vol. 219. no. 4586, pp. 871 - 873
DOI: 10.1126/science.6823554
Prev | Table of Contents | Next

Articles

Science, Vol 219, Issue 4586, 871-873
Copyright © 1983 by American Association for the Advancement of Science

articles

Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages

SK Basu, JL Goldstein, and MS Brown

Cholesterol-loaded macrophages secrete cholesterol and apolipoprotein E. The current studies show that this secretion occurs by two independent pathways. In the absence of serum, the cells secrete apolipoprotein E, but not cholesterol. In the presence of monensin (an inhibitor of protein secretion), the cells secrete cholesterol, but little apolipoprotein E. After secretion, apolipoprotein E and cholesterol associate with high-density lipoprotein to form a particle that can deliver cholesterol to the liver by receptor-mediated endocytosis. We conclude that apolipoprotein E does not function to remove cholesterol from macrophages but rather to participate in "reverse cholesterol transport."


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Regulation of Endogenous Apolipoprotein E Secretion by Macrophages.
M. Kockx, W. Jessup, and L. Kritharides (2008)
Arterioscler Thromb Vasc Biol 28, 1060-1067
   Abstract »    Full Text »    PDF »
Characterization of a new mouse model for human apolipoprotein A-I/C-III/A-IV deficiency.
H. Mezdour, G. Larigauderie, G. Castro, G. Torpier, J. Fruchart, M. Nowak, J.-C. Fruchart, M. Rouis, and N. Maeda (2006)
J. Lipid Res. 47, 912-920
   Abstract »    Full Text »    PDF »
ApoE-mediated cholesterol efflux from macrophages: separation of autocrine and paracrine effects.
D. E. Dove, M. F. Linton, and S. Fazio (2005)
Am J Physiol Cell Physiol 288, C586-C592
   Abstract »    Full Text »    PDF »
Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification.
T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth (2004)
Endocr. Rev. 25, 629-672
   Abstract »    Full Text »    PDF »
Apolipoprotein A-I-stimulated Apolipoprotein E Secretion from Human Macrophages Is Independent of Cholesterol Efflux.
M. Kockx, K.-A. Rye, K. Gaus, C. M. Quinn, J. Wright, T. Sloane, D. Sviridov, Y. Fu, D. Sullivan, J. R. Burnett, et al. (2004)
J. Biol. Chem. 279, 25966-25977
   Abstract »    Full Text »    PDF »
Apolipoprotein E (ApoE) Isoform-dependent Lipid Release from Astrocytes Prepared from Human ApoE3 and ApoE4 Knock-in Mice.
J.-S. Gong, M. Kobayashi, H. Hayashi, K. Zou, N. Sawamura, S. C. Fujita, K. Yanagisawa, and M. Michikawa (2002)
J. Biol. Chem. 277, 29919-29926
   Abstract »    Full Text »    PDF »
Conditional Disruption of the Peroxisome Proliferator-Activated Receptor {gamma} Gene in Mice Results in Lowered Expression of ABCA1, ABCG1, and apoE in Macrophages and Reduced Cholesterol Efflux.
T. E. Akiyama, S. Sakai, G. Lambert, C. J. Nicol, K. Matsusue, S. Pimprale, Y.-H. Lee, M. Ricote, C. K. Glass, H. B. Brewer Jr., et al. (2002)
Mol. Cell. Biol. 22, 2607-2619
   Abstract »    Full Text »    PDF »
Atherosclerosis in C3H/HeJ Mice Reconstituted With Apolipoprotein E-Null Bone Marrow.
W. Shi, X. Wang, K. Tangchitpiyanond, J. Wong, Y. Shi, and A. J. Lusis (2002)
Arterioscler Thromb Vasc Biol 22, 650-655
   Abstract »    Full Text »    PDF »
Dynamic and stable pools of apoE differ functionally at the HepG2 cell surface.
J. W. Burgess and Y. L. Marcel (2001)
J. Lipid Res. 42, 1413-1420
   Abstract »    Full Text »    PDF »
Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice.
N. Ishimori, K. Iwabuchi, S. Fujii, K. Watano, C. Iwabuchi, M. Ato, H. Chiba, S. Tanaka, A. Kitabatake, and K. Onoé (2001)
J. Leukoc. Biol. 69, 732-740
   Abstract »    Full Text »
High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport.
A. von Eckardstein, J.-R. Nofer, and G. Assmann (2001)
Arterioscler Thromb Vasc Biol 21, 13-27
   Abstract »    Full Text »    PDF »
Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats.
P. Ghosh, E. A Hale, K. Mayur, J. Seddon, and M R. Lakshman (2000)
Am. J. Clinical Nutrition 72, 190-198
   Abstract »    Full Text »    PDF »
Effect of Macrophage-Derived Mouse ApoE, Human ApoE3-Leiden, and Human ApoE2 (Arg158->Cys) on Cholesterol Levels and Atherosclerosis in ApoE-Deficient Mice.
M. Van Eck, N. Herijgers, K. W. Van Dijk, L. M. Havekes, M. H. Hofker, P. H. E. Groot, and T. J. C. Van Berkel (2000)
Arterioscler Thromb Vasc Biol 20, 119-127
   Abstract »    Full Text »    PDF »
Apolipoprotein A-I Stimulates Secretion of Apolipoprotein E by Foam Cell Macrophages.
D. Rees, T. Sloane, W. Jessup, R. T. Dean, and L. Kritharides (1999)
J. Biol. Chem. 274, 27925-27933
   Abstract »    Full Text »    PDF »
Vimentin-dependent utilization of LDL-cholesterol in human adrenal tumor cells is not associated with the level of expression of apoE, sterol carrier protein-2, or caveolin.
T. A. Holwell, S. C. Schweitzer, M. E. Reyland, and R. M. Evans (1999)
J. Lipid Res. 40, 1440-1452
   Abstract »    Full Text »
Retroviral Gene Therapy in ApoE-Deficient Mice : ApoE Expression in the Artery Wall Reduces Early Foam Cell Lesion Formation.
A. H. Hasty, M. F. Linton, S. J. Brandt, V. R. Babaev, L. A. Gleaves, and S. Fazio (1999)
Circulation 99, 2571-2576
   Abstract »    Full Text »    PDF »
Elimination of macrophage-specific apolipoprotein E reduces diet-induced atherosclerosis in C57BL/6J male mice.
W. A. Boisvert and L. K. Curtiss (1999)
J. Lipid Res. 40, 806-813
   Abstract »    Full Text »
Regulated turnover of a cell surface-associated pool of newly synthesized apolipoprotein E in HepG2 cells.
M. Schmitt and T. Grand-Perret (1999)
J. Lipid Res. 40, 39-49
   Abstract »    Full Text »
Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells.
J. K. Bielicki, M. R. McCall, and T. M. Forte (1999)
J. Lipid Res. 40, 85-92
   Abstract »    Full Text »
Low-dose expression of a human apolipoprotein E transgene in macrophages restores cholesterol efflux capacity of apolipoprotein E-deficient mouse plasma.
Y. Zhu, S. Bellosta, C. Langer, F. Bernini, R. E. Pitas, R. W. Mahley, G. Assmann, and A. von Eckardstein (1998)
PNAS 95, 7585-7590
   Abstract »    Full Text »    PDF »
Apolipoprotein E {epsilon}2 Allele and Risk of Stroke in the Older Population.
L. Ferrucci, J. M. Guralnik, M. Pahor, T. Harris, M.-C. Corti, M.-C. MHS, B. T. Hyman, R. B. Wallace, and R. J. Havlik (1997)
Stroke 28, 2410-2416
   Abstract »    Full Text »
High-Density Lipoprotein-Binding Protein (HBP)/Vigilin Is Expressed in Human Atherosclerotic Lesions and Colocalizes With Apolipoprotein E.
D. S. Chiu, J. F. Oram, R. C. LeBoeuf, C. E. Alpers, and K. D. O'Brien (1997)
Arterioscler Thromb Vasc Biol 17, 2350-2358
   Abstract »    Full Text »
Effects of Genotype and Diet on Cholesterol Efflux into Plasma and Lipoproteins of Normal, Apolipoprotein A-I-, and Apolipoprotein E-Deficient Mice.
Y. Huang, Y. Zhu, C. Langer, M. Raabe, S. Wu, B. Wiesenhutter, U. Seedorf, N. Maeda, G. Assmann, and A. von Eckardstein (1997)
Arterioscler Thromb Vasc Biol 17, 2010-2019
   Abstract »    Full Text »
Lysophosphatidylcholine Promotes Cholesterol Efflux From Mouse Macrophage Foam Cells.
S. Hara, T. Shike, N. Takasu, and T. Mizui (1997)
Arterioscler Thromb Vasc Biol 17, 1258-1266
   Abstract »    Full Text »
Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.
S. Fazio, V. R. Babaev, A. B. Murray, A. H. Hasty, K. J. Carter, L. A. Gleaves, J. B. Atkinson, and M. F. Linton (1997)
PNAS 94, 4647-4652
   Abstract »    Full Text »    PDF »
Cyclic AMP Induces Apolipoprotein E Binding Activity and Promotes Cholesterol Efflux from a Macrophage Cell Line to Apolipoprotein Acceptors.
J. D. Smith, M. Miyata, M. Ginsberg, C. Grigaux, E. Shmookler, and A. S. Plump (1996)
J. Biol. Chem. 271, 30647-30655
   Abstract »    Full Text »    PDF »
Apolipoprotein E Produced by Human Monocyte-derived Macrophages Mediates Cholesterol Efflux That Occurs in the Absence of Added Cholesterol Acceptors.
W.-Y. Zhang, P. M. Gaynor, and H. S. Kruth (1996)
J. Biol. Chem. 271, 28641-28646
   Abstract »    Full Text »    PDF »
Quantitative Assessment of Aortic Atherosclerosis in APOE*3 Leiden Transgenic Mice and Its Relationship to Serum Cholesterol Exposure.
P. H.E. Groot, B. J.M. van Vlijmen, G. M. Benson, M. H. Hofker, R. Schiffelers, M. Vidgeon-Hart, and L. M. Havekes (1996)
Arterioscler Thromb Vasc Biol 16, 926-933
   Abstract »    Full Text »
Apolipoproteins B, (a), and E Accumulate in the Morphologically Early Lesion of `Degenerative' Valvular Aortic Stenosis.
K. D. O'Brien, D. D. Reichenbach, S. M. Marcovina, J. Kuusisto, C. E. Alpers, and C. M. Otto (1996)
Arterioscler Thromb Vasc Biol 16, 523-532
   Abstract »    Full Text »
Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation.
M. Linton, J. Atkinson, and S Fazio (1995)
Science 267, 1034-1037
   Abstract »    PDF »
Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.
R. Mahley (1988)
Science 240, 622-630
   Abstract »    PDF »
Cellular and Molecular Biology of Lipoprotein Metabolism: Characterization of Lipoprotein Receptor-Ligand Interactions.
R.W. Mahley, T.L. Innerarity, K.H. Weisgraber, S.C. Rall Jr., D.Y. Hui, A. Lalazar, J.K. Boyles, J.M. Taylor, and B. Levy-Wilson (1986)
Cold Spring Harb Symp Quant Biol 51, 821-828
   Abstract »    PDF »
Isolation and Characterization of Apolipoproteins from Murine Microglia. IDENTIFICATION OF A LOW DENSITY LIPOPROTEIN-LIKE APOLIPOPROTEIN J-RICH BUT E-POOR SPHERICAL PARTICLE.
Q. Xu, Y. Li, C. Cyras, D. A. Sanan, and B. Cordell (2000)
J. Biol. Chem. 275, 31770-31777
   Abstract »    Full Text »    PDF »
Caveolin-1 and Caveolin-2 Expression in Mouse Macrophages. HIGH DENSITY LIPOPROTEIN 3-STIMULATED SECRETION AND A LACK OF SIGNIFICANT SUBCELLULAR CO-LOCALIZATION.
P. Gargalovic and L. Dory (2001)
J. Biol. Chem. 276, 26164-26170
   Abstract »    Full Text »    PDF »
Atherosclerosis in C3H/HeJ Mice Reconstituted With Apolipoprotein E-Null Bone Marrow.
W. Shi, X. Wang, K. Tangchitpiyanond, J. Wong, Y. Shi, and A. J. Lusis (2002)
Arterioscler Thromb Vasc Biol 22, 650-655
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)