The state of macrophage differentiation determines the TNFα response to nitrated lipoprotein uptake

Smythe, Cheryl; Skinner, Vernon; Bruckdorfer, K. Richard; Haskard, Dorian O.; Landis, R. Clive

doi:10.1016/s0021-9150(03)00285-5

Cited by 25 publications

(11 citation statements)

References 47 publications

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“…16 oxLDL was prepared by incubation of 100 µg protein/ ml LDL with 5 µmol/l CuSO 4 for 2 hours at 37°C. FITC-conjugated lipoproteins were prepared as described by Smythe et al 17 MPMs were incubated at 37°C for 3 hours with FITC-conjugated native LDL or ox-LDL at a final concentration of 25 µg protein/ml. Cellular uptake of these lipoproteins was determined by fluorescence (excitation at 480 nm, emission at 520 nm) using BD FACSCalibur flow cytometer (BD Biosciences, San Jose, CA, USA).…”

Section: Ldl and Oxidized Ldl (Oxldl) Uptake By Mpmmentioning

confidence: 99%

Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice

Raz-Pasteur

Gamliel-Lazarovich

Gantman

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction: A low-sodium diet (LSD) was shown to increase both angiotensin II (AngII) and aldosterone levels, and to accelerate atherosclerosis in apolipoprotein E-deficient (E0) mice. The aim of the present study was to examine whether accelerated atherosclerosis in E0 mice fed a LSD is mediated by aldosterone, using the mineralocorticoid receptor blocker, eplerenone (Epl). Methods and Results:Mice were divided into three groups: normal diet (ND), LSD and LSD treated with Epl at 100 mg/ kg per day (LSD+Epl) for 10 weeks. LSD significantly enhanced plasma renin and aldosterone levels, which were further increased in mice fed LSD+Epl. The aortic lesion area increased three-fold with LSD, while LSD+Epl significantly reduced the lesion area to values similar to ND. Serum and peritoneal macrophages obtained from LSD-fed mice exhibited proatherogenic properties including increased inflammation, oxidation and cholesterol accumulation, which were inhibited in mice fed LSD+Epl. In a J774A.1 macrophage-like cell line stimulated with lipopolysaccharide, Epl was shown to have a direct anti-inflammatory effect. Conclusion: In E0 mice, Epl inhibited LSD-accelerated atherosclerosis, despite the elevation of renin and aldosterone levels. It is therefore suggested that the atherogenic action of LSD could be mediated, at least in part, by activation of the mineralocorticoid receptor. In addition, eplerenone may have direct anti-inflammatory actions.

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Section: Ldl and Oxidized Ldl (Oxldl) Uptake By Mpmmentioning

confidence: 99%

Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice

Raz-Pasteur

Gamliel-Lazarovich

Gantman

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…CD163 and L-selectin expression were measured in the FL-1 and FL-2 channels, respectively. For ligand-binding studies, Hb:Hp complexes were initially FITC conjugated, as previously described, 32 before incubating with in vitro differentiated macrophages in 24-well plates at 100 g/mL for 2 hours in the presence and absence of blocking RM3/1 antibody (20 g/mL) or control anti-CD64 antibody (20 g/mL). Flow cytometric analysis was carried out using an EPICS XL-3 cytometer (Beckman Coulter).…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis

Philippidis

Mason

Evans

et al. 2004

Circulation Research

430

211

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Abstract-The recently described hemoglobin scavenger receptor CD163 mediates the endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been indirectly associated with antiinflammatory and atheroprotective activity, no ligand-receptor-effector pathway has yet been described for this receptor. To understand the significance of CD163 and more clearly define downstream pathways linked to inflammatory resolution, we studied the expression and function of CD163 in human monocytes/macrophages using both in vitro and in vivo models. Differentiation of human blood monocytes into macrophages either by in vitro culture or in resolving cantharidin-induced skin blisters led to an equivalent increase (Ͼ15ϫ) in CD163 expression. Elevated CD163 levels were also noted on circulating monocytes in cardiac surgical patients during the resolution phase of the systemic inflammatory response to cardiopulmonary bypass surgery. In each case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10 secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo 24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results identify novel antiinflammatory and cytoprotective effector pathways in human monocytes/macrophages related to Hb scavenging and metabolism, which may have relevance in atheroprotection, wound healing, and patient recovery postoperatively.

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“…Lipoproteins (LDL and VLDL) were labelled with FITC as previously described [46]. Briefly, the lipoproteins (protein concentration for LDL was 1 mg/ml and 0.8 mg/mL for VLDL) were dialyzed overnight at 4°C against several changes of borate buffer containing 0.1 M borate, 25 mM sodium tetraborate, 75 mM NaCl, pH 8.6.…”

Section: Lipoprotein Labellingmentioning

confidence: 99%

Atherogenicity of Monosaccharides, Disaccharides and Artificial Sweeteners in the Lipid-Laden Macrophage Model System: Cell Culture and Mice Studies

Na¹,

Hamoud²,

Aviram³

et al. 2017

J Hortic

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IntroductionAtherosclerosis is the underlying cause of cardiovascular diseases (CVD), the major cause of death worldwide [1,2]. Atherosclerosis is an inflammatory disease of the arteries in which activated macrophages are abundant in the atherosclerotic lesions [3]. Macrophages and their oxidative status play key roles during early atherogenesis [3,4]. After differentiating from peripheral monocytes, the formed intimal macrophages incorporate oxidized lipoproteins and are transformed into lipid-rich foam cells, the hallmark feature of early atherosclerosis [3]. In addition to lipoprotein uptake, lipid accumulation in macrophages can also result from alterations in cellular lipid metabolism, e.g. attenuated reverse cholesterol transport or enhanced rates of lipid biosynthesis; all are considerably affected by the oxidative status of the cells [4].High intake of added sugars increases the risk of CVD and type 2 diabetes mellitus (T2DM) [5]. T2DM and hyperglycemia are associated with accelerated atherosclerosis mediated by enhanced macrophage foam cell formation [6]. Numerous studies have demonstrated the detrimental role of high glucose on macrophage oxidative status or lipid metabolism leading to foam cell formation. Accelerated atherosclerosis in diabetic mice was associated with macrophage lipid peroxidation and increased generation of reactive oxygen species (ROS) via induction of NADPH oxidase [7,8]. In addition, macrophages from diabetic mice or under high glucose conditions exhibit lipid accumulation mediated by various mechanisms that regulate intracellular lipid metabolism [7][8][9][10][11][12][13][14][15]. These include enhanced uptake of oxidized (ox)-LDL via up-regulation of the scavenger receptors CD36 and SR-A [7-9,11], enhanced cholesterol or triglyceride biosynthesis rates via induction of lipid biosynthesis regulators e.g. the sterol regulator elements binding proteins (SREBPs), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or diacylglycerol acyltransferase1 (DGAT1) [12,14], and attenuation of HDL-mediated cholesterol efflux from macrophages via suppression of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 [10,13,15].Although the pro-oxidative and pro-atherogenic role of glucose in macrophage foam cell formation has been established, little is Abstract Background: Glucose is known to enhance macrophage foam cell formation and atherosclerosis development. However, the role of other monosaccharides, disaccharides or artificial sweeteners in macrophage atherogenicity remains unclear.

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The state of macrophage differentiation determines the TNFα response to nitrated lipoprotein uptake

Cited by 25 publications

References 47 publications

Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice

Mineralocorticoid receptor blockade inhibits accelerated atherosclerosis induced by a low sodium diet in apolipoprotein E-deficient mice

Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme Oxygenase-1 Synthesis

Atherogenicity of Monosaccharides, Disaccharides and Artificial Sweeteners in the Lipid-Laden Macrophage Model System: Cell Culture and Mice Studies

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