标题：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.
出版社：American Society for Biochemistry and Molecular Biology
摘要：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.
