title: Anti-bis(monoacylglycero)phosphate antibody accumulates acetylated LDL-derived cholesterol in cultured macrophages.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U585, Institut National des Sciences Appliquees-Lyon, Institut Multidisciplinaire de Biochimie des Lipides, 69621 Villeurbanne, France. isabelle.vandenbroucke@insa-lyon.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Delton-Vandenbroucke
authors.forename: Jerome
authors.initials: J
authors.lastname: Bouvier
authors.forename: Asami
authors.initials: A
authors.lastname: Makino
authors.forename: Nelly
authors.initials: N
authors.lastname: Besson
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Pageaux
authors.forename: Michel
authors.initials: M
authors.lastname: Lagarde
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D004951:Esterification / Q000187:drug effects; D005372:Filipin / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008246:Lysophospholipids / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D050178:Monoglycerides / Q000276:immunology*
chemical_list: D000906:Antibodies; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D050178:Monoglycerides; C032629:acetyl-LDL; C012786:bis(monoacylglyceryl)phosphate; D005372:Filipin