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Journal of Lipid Research, Vol 35, 1345-1353, Copyright © 1994 by Lipid Research, Inc.
ARTICLES |
T Mazzone and C Reardon
Department of Medicine, Rush Medical College, Chicago, IL 60612.
Expression of apolipoprotein (apo) E by macrophages is tightly regulated by cellular cholesterol content. We have investigated a potential modulating role for apoE on macrophage cholesterol homeostasis by stably transfecting the J774 macrophage, which does not express its endogenous apoE gene, with a human apoE cDNA expression vector and comparing cholesterol homeostasis in this cell line with that of a control line transfected with the neomycin resistance construct only. Incubation in serum-free medium after cholesterol loading produced no difference in cellular cholesterol content between apoE secreting and non-secreting J774 cells. Similarly, in serum-free medium there was no difference in the amount of radiolabeled cholesterol effluxed. Addition of cAMP or S58035 to cholesterol-loaded J774 cells did enhance efflux of radiolabeled cholesterol from apoE secreting compared to non-secreting macrophages but did not detectably alter cellular free cholesterol or cholesteryl ester mass. Incubation with HDL3 alone, however, significantly decreased macrophage cholesteryl ester mass compared to a 24-h incubation in serum-free medium from 10.5 +/- 3.9 to 3.2 +/- 2.0 (P < 0.01) in apoE-secreting J774 cells. During a 24-h incubation in HDL3, cholesteryl ester fell from 6.4 +/- 2.4 to 0.8 +/- 0.7 (delta = 5.6 micrograms/mg) in apoE- secreting cells and from 9.3 +/- 2.2 to 7.7 +/- micrograms/mg (delta = 1.6 micrograms/mg) in non-secreting cells (P < 0.005 apoE-secreting vs. non-secreting cells).(ABSTRACT TRUNCATED AT 250 WORDS)
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S. Fazio, V. R. Babaev, A. B. Murray, A. H. Hasty, K. J. Carter, L. A. Gleaves, J. B. Atkinson, and M. F. Linton Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages PNAS, April 29, 1997; 94(9): 4647 - 4652. [Abstract] [Full Text] [PDF]
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W. L. Hendriks, F. van der Sman-de Beer, B. J.M. van Vlijmen, L. C. van Vark, M. H. Hofker, and L. M. Havekes Uptake by J774 Macrophages of Very-Low-Density Lipoproteins Isolated From ApoE-Deficient Mice Is Mediated by a Distinct Receptor and Stimulated by Lipoprotein Lipase Arterioscler. Thromb. Vasc. Biol., March 1, 1997; 17(3): 498 - 504. [Abstract] [Full Text]
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