Role of HDL in cholesteryl ester metabolism of lipopolysaccharide-activated P388D1 macrophages

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 macro phages 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/nd enh/nced interleukin 6 secretion. These results imply th/t, besides de novo biosynthesis/nd/cquisition by LDL, HDL contributes prob/bly through SR-B1 to the incre/sed CE content in m/croph/ges, p/rtly expl/ining the low levels of C-HDL during their/ctiv/tion. Our d/t/suggest th/t in those conditions where more CEs/re required, HDL r/ther th/n removing, m/y supply CEs to the cells.