Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Villiers, Willem J.S. de; Smith, J. D.; Miyata, Masaaki; Dansky, Hayes M.; Darley, Elizabeth; Gordon, Siamon

doi:10.1161/01.atv.18.4.631

Cited by 73 publications

(47 citation statements)

References 63 publications

(56 reference statements)

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“…It also augments SR-A, cytokine and growth factor expression and serves as a survival stimulus. Mice deficient in M-CSF are relatively resistant to atherosclerosis [67,68]. Both granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF and G-CSF) increase lesion formation when administered to ApoE knockout mice [69][70][71].…”

Section: Macrophage Development Adhesion and Migration: Steps Towardmentioning

confidence: 99%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

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Subclinical inflammation is a candidate etiological factor in the pathogenesis of metabolic syndrome and in the progression of atherosclerosis. A central role for activated macrophages has been elucidated recently as important regulators of the inflammatory process in atherosclerosis. Macrophage differentiation and function can be modulated by a class of transcription factors termed nuclear receptors. These are activated by intermediary products of basic metabolic processes. In this review the contribution of peroxisome proliferator-activated receptors and liver X receptors to macrophage functions in inflammation and lipid metabolism will be discussed in light of their roles in macrophages during atherosclerosis.In the past decade much effort has been made to understand the mechanisms how lipids are handled by macrophages and how inflammation could promote the atherogenic process. Here, we also provide an overview of these two fields.

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Section: Macrophage Development Adhesion and Migration: Steps Towardmentioning

confidence: 99%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

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“…Interest in MS as a scavenger and oxLDL receptor arose when it was suggested, on the basis of ligand blotting, to bind oxLDL (18,19). Further evidence for a role for MS in modified LDL catabolism includes its identification in liver Kupffer cells as the major oxLDL binding protein (20), and its prominent expression in macrophages in atherosclerotic plaques from apoE knockout mice (21).…”

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confidence: 99%

Lack of a direct role for macrosialin in oxidized LDL metabolism

Beer

Zhao

Webb

et al. 2003

Journal of Lipid Research

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Murine macrosialin (MS), a scavenger receptor family member, is a heavily glycosylated transmembrane protein expressed predominantly in macrophage late endosomes. MS is also found on the cell surface where it is suggested, on the basis of ligand blotting, to bind oxidized LDL (oxLDL). Here we report on the regulation of MS by an atherogenic high-fat diet and oxLDL, and on the inability of MS in transfected cells to bind oxLDL. MS expression was markedly increased in the livers of atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant C3H/HeJ mice fed an atherogenic high-fat diet. In resident-mouse peritoneal macrophages, treatment with oxLDL upregulated MS mRNA and protein expression 1. There is accumulating evidence that oxidative modifications of LDL contribute to early atherogenesis (1). The uncontrolled uptake of modified and oxidized LDL (oxLDL) by vascular wall macrophages in the subendothelial space via scavenger receptors produces excessive lipoprotein-derived cholesteryl ester (CE) accumulations characteristic of foam cell formation. Macrophage-derived foam cells are the hallmark of fatty streaks and atherosclerotic plaques in human disease and in animal models of atherosclerosis. A number of different macrophage cell surface scavenger receptors for modified LDL have now been identified (2), and key questions are the relative contribution of the different macrophage scavenger receptors to atherogenesis and whether they play a protective role to clear oxidized lipids, as opposed to a pathological role in lesion development.Data from studies with scavenger receptor class A (SR-A) gene knockout animals indicate that SR-A acts as a proatherogenic molecule in vivo (3, 4). This effect is modest, however, and requires backcrosses on atherosclerosis-susceptible apolipoprotein E (apoE)-deficient ( Ϯ 50% reduced relative to apoE Ϫ / Ϫ ) (3) or LDL receptor (LDLR) knockout animals ( Ϯ 20% reduced relative to LDLR Ϫ / Ϫ ) (4) to become apparent. There was no difference in the plasma clearance of acetylated LDL or oxLDL when SR-A-deficient animals were compared with wild-type animals (3). Recent studies have also shown that C57BL/6 mice lacking SR-A are protected from diet-induced atherosclerosis; furthermore, SR-A expression specifically in macrophages contributes significantly to lesion formation in C57BL/6 and LDLR null mice (5). These data support a role for SR-A in atherogenesis, but also indicate that macrophage scavenger receptors other than SR-A participate in the in vivo generation of foam cells.CD36 is involved in the endocytosis of long-chain fatty acids, anionic phospholipids, and oxidized lipoproteins (6). CD36-null mice have increased fasting plasma cholesterol, and increased nonesterified free fatty acid and triacylglycerol levels. CD36-apoE double null mice have markedly decreased aortic lesions, both on normal and Western diet, when compared with controls, despite alterations in lipoproteins that correlate with increased atherogenicity (7,8). Macrophages from CD36-apoE double kno...

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“…Among the components of innate immunity, monocyte-derived macrophages are present in abundance at all stages of the disease process. 1 Their pivotal role in atherogenesis has been demonstrated by the attenuation of lesion formation in monocyte deficiency in both apolipoprotein E Ϫ/Ϫ mice 35 and ldl-r Ϫ/Ϫ mice. 36 Two other cellular components of innate immunity for which there is a paucity of information regarding their atherogenic role are neutrophils and NK cells.…”

Section: Discussionmentioning

confidence: 99%

Depletion of Natural Killer Cell Function Decreases Atherosclerosis in Low-Density Lipoprotein Receptor Null Mice

Whitman

Rateri

Szilvassy

et al. 2004

ATVB

132

104

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Objective-Natural killer (NK) cells are a key component of innate immunity. Despite being identified in human and mouse atherosclerotic lesions, the role of NK cells in the disease process in unknown. To determine this role, we created chimeric atherosclerosis-susceptible low-density lipoprotein (LDL) receptor null (ldl-r Ϫ/Ϫ ) mice that were deficient in functional NK cells through expression of a transgene encoding for Ly49A. Methods and Results-Bone marrow cells from Ly49A transgenic and nontransgenic littermates were used to repopulate the hematopoietic system of lethally-irradiated female ldl-r Ϫ/Ϫ mice. After a recovery period to permit sufficient engraftment, mice were placed on a diet enriched in saturated fat and cholesterol. After 8 weeks, there was no difference in either serum total cholesterol concentrations or lipoprotein cholesterol distribution in mice repopulated with nontransgenic versus Ly49A transgenic marrow cells. Using immunohistochemistry, we detected NK cells in atherosclerotic lesions of both groups of mice. However, deficiency of functional NK cells significantly reduced the size of atherosclerosis by 70% (Pϭ0.0002) in cross-sectional analysis of the aortic root and by 38% (Pϭ0.004) in en face analysis of the intimal surface of the aortic arch. Conclusion-These

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Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Cited by 73 publications

References 63 publications

Nuclear receptors in macrophages: A link between metabolism and inflammation

Nuclear receptors in macrophages: A link between metabolism and inflammation

Lack of a direct role for macrosialin in oxidized LDL metabolism

Depletion of Natural Killer Cell Function Decreases Atherosclerosis in Low-Density Lipoprotein Receptor Null Mice

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