J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol 37, 2155-2166, Copyright © 1996 by Lipid Research, Inc.


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Phagocytosis of mast cell granule remnant-bound LDL by smooth muscle cells of synthetic phenotype: a scavenger receptor-mediated process that effectively stimulates cytoplasmic cholesteryl ester synthesis

Y Wang, KA Lindstedt and PT Kovanen
Wihuri Research Institute, Helsinki, Finland.

Mast cell granule remnants contain heparin proteoglycans and bind low density lipoproteins (LDL). Phagocytosis of such LDL-coated remnants by smooth muscle cells of synthetic phenotype (s-SMC) leads to cellular accumulation of LDL-derived cholesteryl esters (Wang et al. 1995. Arterioscler. Thromb. Vasc. Biol. 15: 801-810). In the present study, we investigated the pathway by which granule remnants mediate the uptake of LDL by s-SMC and the effect of the remnants on the metabolism of LDL-derived cholesteryl esters in these cells. In vitro, the scavenger receptor ligands polyinosinic acid, acetylated LDL (AcLDL), and oxidized LDL (OxLDL) each inhibited the uptake of granule remnant- bound LDL maximally by 50-60%. When AcLDL and OxLDL were added as a mixture, uptake was totally inhibited. Conversely, the granule remnants inhibited the binding of AcLDL to s-SMC. We also found that granule remnants did not inhibit the lysosomal hydrolysis of LDL-derived cholesteryl esters in s-SMC. When s-SMC were incubated with LDL in the presence of granule remnants, the cellular contents of cholesteryl linoleate and cholesteryl oleate increased. These increases were retarded when an inhibitor of acyl-CoA:cholesterol acyl-transferase (ACAT) was present, showing that the cholesteryl ester accumulation in the s-SMC was a cytoplasmic process due to reesterification of LDL- derived cholesterol and fatty acids. In summary, exocytosed mast cell granule remnants carry LDL into s-SMC by scavenger receptor-mediated phagocytosis, and induce formation of typical foam cells, filled with cytoplasmic cholesteryl ester droplets.
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Y. Wang and P. T. Kovanen
Heparin Proteoglycans Released From Rat Serosal Mast Cells Inhibit Proliferation of Rat Aortic Smooth Muscle Cells in Culture
Circ. Res., January 22, 1999; 84(1): 74 - 83.
[Abstract] [Full Text] [PDF]




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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.