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Journal of Lipid Research, Vol 37, 2155-2166, Copyright © 1996 by Lipid Research, Inc.
Y Wang, KA Lindstedt and PT Kovanen
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.
ARTICLES
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
Wihuri Research Institute, Helsinki, Finland.
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