HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rees, D. Articles by Kritharides, L. Search for Related Content PubMed PubMed Citation Articles by Rees, D. Articles by Kritharides, L. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 39, 27925-27933, September 24, 1999

Apolipoprotein A-I Stimulates Secretion of Apolipoprotein E by Foam Cell Macrophages

David Rees, Timothy Sloane^¶, Wendy Jessup, Roger T. Dean, and Leonard Kritharides^¶

From the  Cell Biology and ^¶ Clinical Research Groups, Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, New South Wales 2050 and the  Department of Cardiology, Concord Hospital, University of Sydney, Hospital Road, Concord, Sydney, New South Wales 2139, Australia

Apolipoprotein A-I (apoA-I) overexpression inhibits atherogenesis in mice, and apolipoprotein E (apoE) secreted by foam cell macrophages may exert antiatherogenic effects within the arterial wall. We hypothesized that interaction between apoA-I and apoE contributed to the antiatherogenic properties of apoA-I, and therefore investigated whether apoA-I stimulated secretion of apoE by foam cell macrophages. Cholesterol enrichment of primary murine and human macrophages increased spontaneous apoE secretion 2-fold, as quantified by Western blot and chemiluminescence detection. Human apoA-I caused a further marked increase of apoE secretion from both murine (3.8-fold, p < 0.01) and human (3.2-fold, p = 0.01) foam cells in a time- and concentration- dependent manner, and this increase was confirmed by immunoprecipitation of [³⁵S]methionine-labeled macrophage apoE. The protein synthesis inhibitor cycloheximide, but not the transcription inhibitor actinomycin D, markedly inhibited apoE secretion to apoA-I (73.1 ± 9.8% inhibition at 4 h) and completely suppressed apoE secretion beyond 4 h. Pretreatment of macrophages with Pronase inhibited initial apoA-I-mediated apoE secretion by 70.5 ± 6.5% at 2 h, but by 8 h apoA-I-induced apoE secretion was the same in Pronase-pretreated and non-pretreated cells. Non-apolipoprotein-mediated cholesterol efflux induced by trimethyl- cyclodextrin did not enhance apoE secretion, whereas phospholipid vesicles inducing the same degree of cholesterol efflux substantially enhanced apoE secretion, and apoA-I and phospholipid vesicles in combination demonstrated additive induction of apoE secretion. We conclude that apoA-I concurrently stimulates apoE secretion and cholesterol efflux from foam cell macrophages and that lipoprotein-derived apoA-I may enhance local secretion and accumulation of apoE in atherosclerotic lesions.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Kockx, W. Jessup, and L. Kritharides Regulation of Endogenous Apolipoprotein E Secretion by Macrophages Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1060 - 1067. [Abstract] [Full Text] [PDF]

				M. Kockx, D. L. Guo, T. Huby, P. Lesnik, J. Kay, T. Sabaretnam, E. Jary, M. Hill, K. Gaus, J. Chapman, et al. Secretion of Apolipoprotein E From Macrophages Occurs via a Protein Kinase A and Calcium-Dependent Pathway Along the Microtubule Network Circ. Res., September 14, 2007; 101(6): 607 - 616. [Abstract] [Full Text] [PDF]

				I. C. Gelissen, M. Harris, K.-A. Rye, C. Quinn, A. J. Brown, M. Kockx, S. Cartland, M. Packianathan, L. Kritharides, and W. Jessup ABCA1 and ABCG1 Synergize to Mediate Cholesterol Export to ApoA-I Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 534 - 540. [Abstract] [Full Text] [PDF]

				A. H. Hasty, M. R. Plummer, K. H. Weisgraber, M. F. Linton, S. Fazio, and L. L. Swift The recycling of apolipoprotein E in macrophages: influence of HDL and apolipoprotein A-I J. Lipid Res., July 1, 2005; 46(7): 1433 - 1439. [Abstract] [Full Text] [PDF]

				M. S. Spagnuolo, L. Cigliano, L. D. D'Andrea, C. Pedone, and P. Abrescia Assignment of the Binding Site for Haptoglobin on Apolipoprotein A-I J. Biol. Chem., January 14, 2005; 280(2): 1193 - 1198. [Abstract] [Full Text] [PDF]

				J. Heeren, T. Grewal, A. Laatsch, N. Becker, F. Rinninger, K.-A. Rye, and U. Beisiegel Impaired Recycling of Apolipoprotein E4 Is Associated with Intracellular Cholesterol Accumulation J. Biol. Chem., December 31, 2004; 279(53): 55483 - 55492. [Abstract] [Full Text] [PDF]

				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. Apolipoprotein A-I-stimulated Apolipoprotein E Secretion from Human Macrophages Is Independent of Cholesterol Efflux J. Biol. Chem., June 18, 2004; 279(25): 25966 - 25977. [Abstract] [Full Text] [PDF]

				J. Lee, A. Tauscher, D. W. Seo, J. F. Oram, and R. Kuver Cultured gallbladder epithelial cells synthesize apolipoproteins A-I and E Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G630 - G641. [Abstract] [Full Text] [PDF]

				S. M. Liu, A. Cogny, M. Kockx, R. T. Dean, K. Gaus, W. Jessup, and L. Kritharides Cyclodextrins differentially mobilize free and esterified cholesterol from primary human foam cell macrophages J. Lipid Res., June 1, 2003; 44(6): 1156 - 1166. [Abstract] [Full Text] [PDF]

				J. Heeren, T. Grewal, A. Laatsch, D. Rottke, F. Rinninger, C. Enrich, and U. Beisiegel Recycling of Apoprotein E Is Associated with Cholesterol Efflux and High Density Lipoprotein Internalization J. Biol. Chem., April 11, 2003; 278(16): 14370 - 14378. [Abstract] [Full Text] [PDF]

				M. H. Farkas, L. L. Swift, A. H. Hasty, M. F. Linton, and S. Fazio The Recycling of Apolipoprotein E in Primary Cultures of Mouse Hepatocytes. EVIDENCE FOR A PHYSIOLOGIC CONNECTION TO HIGH DENSITY LIPOPROTEIN METABOLISM J. Biol. Chem., March 7, 2003; 278(11): 9412 - 9417. [Abstract] [Full Text] [PDF]

				M. P. Vallely, P. G. Bannon, C. F. Hughes, and L. Kritharides Endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 is suppressed by postbypass plasma containing increased soluble intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 J. Thorac. Cardiovasc. Surg., October 1, 2002; 124(4): 758 - 767. [Abstract] [Full Text] [PDF]

				S. Bultel-Brienne, S. Lestavel, A. Pilon, I. Laffont, A. Tailleux, J.-C. Fruchart, G. Siest, and V. Clavey Lipid Free Apolipoprotein E Binds to the Class B Type I Scavenger Receptor I (SR-BI) and Enhances Cholesteryl Ester Uptake from Lipoproteins J. Biol. Chem., September 20, 2002; 277(39): 36092 - 36099. [Abstract] [Full Text] [PDF]

				A. VON ECKARDSTEIN, C. LANGER, T. ENGEL, I. SCHAUKAL, A. CIGNARELLA, J. REINHARDT, S. LORKOWSKI, Z. LI, X. ZHOU, P. CULLEN, et al. ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages FASEB J, July 1, 2001; 15(9): 1555 - 1561. [Abstract] [Full Text] [PDF]

				A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]

				A. J. Brown, G. F. Watts, J. R. Burnett, R. T. Dean, and W. Jessup Sterol 27-Hydroxylase Acts on 7-Ketocholesterol in Human Atherosclerotic Lesions and Macrophages in Culture J. Biol. Chem., September 1, 2000; 275(36): 27627 - 27633. [Abstract] [Full Text] [PDF]