Anti-bis(monoacylglycero)phosphate antibody accumulates acetylated LDL-derived cholesterol in cultured macrophages

Bis(monoacylglycero)phosphate (BMP), also called lysobisphosphatidic acid, is a phospholipid highly enriched in the internal membranes of multivesicular late endosomes, in which it forms specialized lipid domains. It has been suggested that BMP-rich membranes regulate cholesterol transport. Here, we...

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Published inJournal of lipid research Vol. 48; no. 3; pp. 543 - 52
Main Authors Delton-Vandenbroucke, Isabelle, Bouvier, Jerome, Makino, Asami, Besson, Nelly, Pageaux, Jean-François, Lagarde, Michel, Kobayashi, Toshihide
Format Journal Article
LanguageEnglish
Published American Society for Biochemistry and Molecular Biology 01.03.2007
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Summary:Bis(monoacylglycero)phosphate (BMP), also called lysobisphosphatidic acid, is a phospholipid highly enriched in the internal membranes of multivesicular late endosomes, in which it forms specialized lipid domains. It has been suggested that BMP-rich membranes regulate cholesterol transport. Here, we examine the effects of an anti-BMP antibody on cholesterol metabolism and transport in two macrophage cell lines, RAW 264.7 and THP-1, during loading with acetylated low density lipoprotein (AcLDL). Anti-BMP antibody was internalized and accumulated in both macrophage cell types. Cholesterol staining with filipin and mass measurements indicate that AcLDL-stimulated accumulation of free cholesterol (FC) was enhanced in macrophages that had accumulated the antibody. Unlike the hydrophobic amine U18666A (3-beta-[2-(diethylamino)ethoxy]androst-5-en-17-one), esterification of AcLDL-derived cholesterol by ACAT was not modified after anti-BMP treatment. AcLDL loading led to an increase of FC in the plasma membrane. This increase was further enhanced in anti-BMP-treated macrophages. However, cholesterol efflux to HDL was reduced in antibody-treated cells. These results suggest that the accumulation of anti-BMP antibody alters cholesterol homeostasis in AcLDL-loaded macrophages.
ISSN:0022-2275
DOI:10.1194/jlr.M600266-JLR200