Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.

Aviram, Michael; Williams, Kevin Jon; McIntosh, Rawle M.; Carpentier, Yvon; Tall, Alan R.; Deckelbaum, Richard J.

doi:10.1161/01.atv.9.1.67

Cited by 41 publications

(12 citation statements)

References 34 publications

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“…(35 μg/100 g body weight), and after 4 h (under light ether anesthesia), animals were bled and killed by carotid section. A macrophage-enriched suspension (containing some mast cells, polymorphonuclear cells, and monocytes) was obtained by peritoneal lavage (Aviram et al 1989). Briefly, the peritoneal cavity was injected with 10 ml cold phosphate-buffered saline (PBS), pH 7.4, and gently massaged for 2 min before removal of a suspension of peritoneal cells that was filtered through a nylon cloth and washed twice with PBS by centrifugation (250g for 10 min at 4°C).…”

Section: Methodsmentioning

confidence: 99%

Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia

Antohe¹,

Rădulescu²,

Puchianu³

et al. 2005

Cell Tissue Res

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In the pathogenesis of atherosclerosis, macrophages become activated and play a crucial role in plaque formation. Activated synovial macrophages have recently been shown to express receptors for folic acid. We have determined whether activated macrophages also over-express folate receptor (FR) in atherosclerosis. Most normal cells express little or no FR, and, if FR is present on activated macrophages, folate-linked compounds and drugs could be selectively targeted to those cells that do express FR. To evaluate the FR on macrophages of atherosclerotic animals, golden Syrian hamsters were maintained on a hyperlipidemic diet until extensive vascular lesions had developed. Uptake of folic acid conjugated to fluorescent tags was then examined in tissue fragments from lesion-prone areas, and peritoneal activated macrophages were harvested from the same animals. Spectrofluorimetric and fluorescence microscopic analyses showed a significantly greater uptake of folate-conjugates by peritoneal macrophages of hyperlipidemic hamsters compared with those of hamsters fed a normal or folate-deficient diet. Systemically administered folate-fluorescent conjugates were found to accumulate as bright spots in protrusions of atherosclerotic plaques populated by macrophages, whereas a low level of fluorescence was detected uniformly dispersed across the lesion. The uptake of the folate conjugate by U937 macrophage cells grown in a high-lipid culture medium was significantly higher than in controls. Our data thus indicate that hyperlipidemic conditions induce an increased uptake of folate attributable to the over-expression of FRs on activated macrophages. This increase in FR expression can be exploited to deliver folate-linked compounds selectively to atherosclerotic lesions.

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Section: Methodsmentioning

confidence: 99%

Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia

Antohe¹,

Rădulescu²,

Puchianu³

et al. 2005

Cell Tissue Res

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“…A solution of -carotene (l g/l) was added to a dispersion of chromatographically pure egg phosphatidylcholine (10 g/1) (Sigma Chemical Co., St. Louis, MO) to give a concentration of 10mg/l -carotene (the solvent volume was therefore 1 % of the total incubation volume). This mixture was sonicated at 4 °C under argon for 20 minutes (x 3) followed by centrifugation (1500g, 10 minutes), and the liposomes were collected by filtration through a 0.45 μηι filter (28). Since carotenoids are very sensitive to light-induced oxidation, all carotene preparations were kept in covered bottles under nitrogen at -20 °C.…”

Section: Methodsmentioning

confidence: 99%

Preferential Inhibition of LDL Oxidation by the all-trans Isomer of β-Carotene in Comparison with 9-cis β-Carotene

Lavy¹,

Amotz²,

Aviram³

1993

Clinical Chemistry and Laboratory Medicine

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Summary:The synthetic all-trans isomer of ß-carotene was recently shown to possess antioxidant properties towards the formation of oxidized low density lipoprotein.| In the present study, the binding of the all-trans and the 9-cis isomers of ß-carotene to plasma lipoproteins was investigated, and the effect of these isomers on the susceptibility of plasma lipoprotein to lipid peroxidation and on macrophage uptake of oxidized LDL were studied. Both the synthetic all-trans isomer of ß-carotene and the natural ß-carotene from the algae Dunaliella Bardawil [which is composed of the all-trans (70%) and 1 the 9-cis (30%) isomers], were found to bind similarly to all plasma lipoproteins, following the incubation of ß-carotene with purified lipoproteins or with whole plasma.Incubation of the ß-carotene isomers with whole plasma, followed by separation of the lipoproteins, revealed substantial carotene binding to very low density lipoprotein (VLDL) and to LDL and limited binding to high density lipoprotein (HDL). Lipid peroxidation of VLDL and LDL were significantly inhibited by ß-carotene.The synthetic ß-carotene, however, was twice as effective as the Dunaliella ß-carotene in inhibiting LDL lipid | peroxidation (following LDL incubation with copper ions). Cellular degradation of oxidized lipoproteins | (mediated via the scavenger receptor) was decreased by 40% and 18%, respectively, when they were prepared by incubation in the presence of synthetic or natural ß-carotene; the control oxidized LDL was prepared in the absence of ß-carotene.ß-Carotene probably binds to the cholesteryl ester moiety of LDL, and causes changes in the physicochemical properties of the lipoprotein. The synthetic all-trans isomer of ß-carotene, but not the natural ß-carotene, reduced LDL electrophoretic mobility and increased the availability of free amino groups of lysine residues.We conclude that altough both the all-trans and the 9-cis isomers of ß-carotene can bind in vitro to plasma ! lipoproteins, they exert different effects of LDL atherogenicity; the all-trans isomer of ß-carotene is more effective in inhibiting the susceptibility of lipoproteins to lipid peroxidation and in reducing the cellular uptake of oxidized LDL by macrophages.

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“…The cells were fed every 3 days (36). Mouse peritoneal macrophages (MPM) were harvested from the peritoneal fluid 4 days after intraperitoneal injection of 3 ml of thioglycolate in saline (24 g/mouse) (37).…”

Section: Cells and Cell Fractionationmentioning

confidence: 99%

Macrophage Enrichment with the Isoflavan Glabridin Inhibits NADPH Oxidase-induced Cell-mediated Oxidation of Low Density Lipoprotein

Rosenblat¹,

Belinky²,

Vaya³

et al. 1999

Journal of Biological Chemistry

108

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Macrophage-mediated oxidation of low density lipoprotein (LDL) is considered to be of major importance in early atherogenesis; therefore, intervention means to inhibit this process are being extensively studied. In the present study, we questioned the ability of the isoflavan glabridin (from licorice) to accumulate in macrophages and to affect cell-mediated oxidation of LDL. We first performed in vitro studies, using mouse peritoneal macrophages (MPMs) and the J-774 A.1 macrophage-like cell line. Both cells accumulated up to 1.5 g of glabridin/mg of cell protein after 2 h of incubation, and this process was time-and glabridin dose-dependent. In parallel, in glabridin-enriched cells, macrophage-mediated oxidation of LDL was inhibited by up to 80% in comparison with control cells. Glabridin inhibited superoxide release from MPMs in response to phorbol 12-myristate 13-acetate, or to LDL when added together with copper ions, by up to 60%. Translocation of P-47, a cytosolic component of NADPH oxidase to the plasma membrane was substantially inhibited. In glabridin-enriched macrophages, protein kinase C activity reduced by ϳ70%. All of the above effects of glabridin required the presence of the two hydroxyl groups on the flavonoid's B phenol ring. In order to assess the physiological significance of these results, we next performed in vivo studies, using the atherosclerotic apolipoprotein E-deficient (E 0 ) mice. MPMs harvested from glabridin-treated E 0 mice (20 g/mouse/day for a period of 6 weeks) demonstrated reduced capability to oxidize LDL by 80% in comparison with placebo-treated mice. This latter phenomenon was associated with a reduction in the lesion oxysterols and a 50% reduction in the aortic lesion size.We thus conclude that glabridin accumulation in macrophages is associated with reduced cell-mediated oxidation of LDL and decreased activation of the NADPH oxidase system. These phenomena could be responsible for the attenuation of atherosclerosis in E 0 mice, induced by glabridin.The LDL 1 oxidation hypothesis of atherosclerosis is supported by evidence for the accumulation of oxidized LDL in the atherosclerotic lesion, by increased LDL oxidizability in patients with increased risk for atherosclerosis, and by the antiatherogenicity of several potent antioxidants against LDL oxidation (1-4). Extensive investigation is being made to identify natural food products that can offer antioxidant defense against LDL oxidation. Flavonoids are polyphenolic compounds naturally present in fruits and vegetables and are an integral part of the human diet (5). Consumption of flavonoids in the diet was shown to be inversely associated with morbidity and mortality from coronary heart disease (6, 7). Flavonoids are powerful antioxidants and their antioxidative capacity is related to their chemical structure (8,9). We have recently shown that dietary supplementation of healthy human volunteers with flavonoid-rich nutrients such as olive oil, red wine, or licorice root, resulted in a reduction in LDL oxidizability (10 -12). F...

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Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.

Cited by 41 publications

References 34 publications

Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia

Increased uptake of folate conjugates by activated macrophages in experimental hyperlipemia

Preferential Inhibition of LDL Oxidation by the all-trans Isomer of β-Carotene in Comparison with 9-cis β-Carotene

Macrophage Enrichment with the Isoflavan Glabridin Inhibits NADPH Oxidase-induced Cell-mediated Oxidation of Low Density Lipoprotein

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