title: Role of HDL in cholesteryl ester metabolism of lipopolysaccharide-activated P388D1 macrophages.
abstract: Infections share with atherosclerosis similar lipid alterations, with accumulation of cholesteryl esters (CEs) in activated macrophages and concomitant decrease of cholesterol-HDL (C-HDL). Yet the precise role of HDL during microbial infection has not been fully elucidated. Activation of P388D1 by lipopolysaccharide (LPS) triggered an increase of CEs and neutral lipid contents, along with a remarkable enhancement in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-HDL uptake. Similar results were found in human monocyte-derived macrophages and monocytes cocultured with phytohemagglutinin-activated lymphocytes. Inhibition of cholesterol esterification with Sandoz-58035 resulted in 80% suppression of CE biosynthesis in P388D1. However, only a 35% decrease of CE content, together with increased scavenger receptor class B member 1 (SR-B1) protein expression, was found after 72 h and thereafter up to 16 passages of continuous ACAT suppression. Chronic inhibition blunted the effect of LPS treatment on cholesterol metabolism, increased the ratio of free cholesterol/CE content and enhanced interleukin 6 secretion. These results imply that, besides de novo biosynthesis and acquisition by LDL, HDL contributes probably through SR-B1 to the increased CE content in macrophages, partly explaining the low levels of C-HDL during their activation. Our data suggest that in those conditions where more CEs are required, HDL rather than removing, may supply CEs to the cells.
authors: Experimental Medicine Unit, University of Cagliari, Cagliari, Italy.
authors: Sabrina
authors: S
authors: Uda
authors: Stefano
authors: S
authors: Spolitu
authors: Fabrizio
authors: F
authors: Angius
authors: Maria
authors: M
authors: Collu
authors: Simonetta
authors: S
authors: Accossu
authors: Sebastiano
authors: S
authors: Banni
authors: Elisabetta
authors: E
authors: Murru
authors: Francesca
authors: F
authors: Sanna
authors: Barbara
authors: B
authors: Batetta
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D016207:Cytokines; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D016328:NF-kappa B; D010835:Phytohemagglutinins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: immune cells; inflammation; microbial stimulus
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