High-Density Lipoprotein Reduces the Human Monocyte Inflammatory Response

Murphy, AJ; Woollard, KJ; Hoang, A; Mukhamedova, N; Stirzaker, RA; McCormick, SPA; Remaley, AT; Sviridov, D; Chin-Dusting, J

Author(s): Murphy, AJ; Woollard, KJ; Hoang, A; Mukhamedova, N; Stirzaker, RA; McCormick, SPA; Remaley, AT; Sviridov, D; Chin-Dusting, J;
Details: Publication Year 2008-11,Volume 28,Issue #11,Page 2071-U313
Journal Title: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Publication Type: Journal Article
Abstract: Objective-Whereas the anti-inflammatory effects of high-density lipoprotein (HDL) on endothelial cells are well described, such effects on monocytes are less studied. Methods and Results-Human monocytes were isolated from whole blood followed by assessment of CD11b activation/expression and cell adhesion under shear-flow. HDL caused a dose-dependent reduction in the activation of CD11b induced by PMA or receptor-dependent agonists. The constituent of HDL responsible for the antiinflammatory effects on CD11b activation was found to be apolipoprotein A-I (apoA-I). Cyclodextrin, but not cyclodextrin/cholesterol complex, also inhibited PMA-induced CD11b activation implicating cholesterol efflux as the main mechanism. This was further confirmed with the demonstration that cholesterol content of lipid rafts diminished after treatment with the cholesterol acceptors. Blocking ABCA1 with an anti-ABCA1 antibody abolished the effect of apoA-I. Furthermore, monocytes derived from a Tangier disease patient definitively confirmed the requirement of ABCA1 in apoA-I mediated CD11b inhibition. The antiinflammatory effects of apoA-I were also observed in functional models including cell adhesion to an endothelial cell monolayer, monocytic spreading under shear flow, and transmigration. Conclusions-HDL and apoA-I exhibit an antiinflammatory effect on human monocytes by inhibiting activation of CD11b. ApoA-I acts through ABCA1, whereas HDL may act through several receptors. (Arterioscler Thromb Vasc Biol. 2008; 28: 2071-2077)
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Keywords: APOLIPOPROTEIN-A-I; HUMAN ENDOTHELIAL-CELLS; CASSETTE TRANSPORTER A1; CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; CHOLESTEROL EFFLUX; ADHESION MOLECULES; HELICAL PEPTIDES; LIPID EFFLUX; ICAM-1 CD54
Publisher's Version: https://doi.org/10.1161/ATVBAHA.108.168690
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-11-01 12:00:00