Different binding of<sup>125</sup>I-LPS to plasma proteins from persons with high or low HDL

Eggesbø, Jan Bertil; Lyberg, T; Aspelin, Trude; Hjermann, Ingvar; Kierulf, Peter

doi:10.3109/00365519609088809

Cited by 25 publications

(21 citation statements)

References 30 publications

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“…The LBP-transporting lipoproteins LDL and VLDL were also found to be the predominant LPS-binding lipoproteins in normal human serum, an observation which is supported by others (5,24). Studies performed in rodents report the preferential binding of LPS to HDL (4,(25)(26)(27).…”

Section: Discussionsupporting

confidence: 65%

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

Vreugdenhil

Snoek²,

Veer³

et al. 2001

J. Clin. Invest.

142

100

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IntroductionLPS is a constituent of the outer membrane of gramnegative bacteria and evokes an inflammatory response by activation of monocytes and endothelial cells. LPSinduced cellular responses are the net result of the interaction of LPS with various plasma components such as soluble CD14, LPS-binding protein (LBP) and membrane receptors such as membrane-bound CD14 and Toll-like receptors. This initiation of cellular responses is essential for the host defense against bacterial infections. However, if large amounts of endotoxin are present in the circulation, an excessive cellular response can be deleterious for the host, and, therefore, endotoxin-inactivating processes are of extreme importance.LPS is detoxified in the circulation by incorporation into lipoproteins (reviewed in ref. 1). Physiological levels of lipoproteins protect against endotoxicity in vitro and in vivo (2, 3). Early studies have demonstrated an interaction of LPS with HDL (4); albeit later, also VLDL and LDL were found to bind and inactivate LPS (5-7). Consistent with this, LDL, VLDL, chylomicrons, and HDL all have been observed to reduce the lethal effect of endotoxin in mice (8-10).Evidence for a physiological role for LBP in inflammation is supported by studies that demonstrate enhanced mortality and uncontrolled multiplication and spread of bacteria in LBP knockout mice compared with wild-type mice after intraperitoneal administration of bacteria (11). The results of these studies indicate that LBP is required to induce a rapid inflammatory response, which is essential for the resistance to bacteria. However, LBP has the paradoxical dual function of sensitizing the immune system to endotoxin and, on the other hand, enhancing detoxification of endotoxin. LBP catalyzes the transfer of LPS into lipoproteins, thereby enhancing LPS detoxification (12). Likewise, LBP catalyzes the lipoprotein neutralization of lipoteichoic acid, a component of the cell membrane of gram-positive bacteria (13). Lamping et al. demonstrated in a murine model that high levels of LBP in the circulation, as seen during an acute-phase response, inhibit LPS effects and prevent mortality induced by endotoxemia (14). The latter observation strongly supports a physiological role for LBP-dependent detoxification of LPS in the host defense.Endotoxemia induces an acute-phase response characterized by multiple physiological adaptations. This response appears to play a role in host defense mechanisms, although its physiological relevance needs further elucidation. One aspect of the acute-phase response is a dramatic rise in circulating levels of LBP LPS-binding protein (LBP) and serum lipoproteins cooperate in reducing the toxic properties of LPS.In the present study, we demonstrate that LBP circulates in association with LDL and VLDL in healthy persons. ApoB was found to account at least in part for the interaction of LBP with LDL and VLDL. Although LBP interacted with purified apoA-I in vitro, no association of LBP with apoA-I or HDL was found in serum. Consistent with th...

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Section: Discussionsupporting

confidence: 65%

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

Vreugdenhil

Snoek²,

Veer³

et al. 2001

J. Clin. Invest.

142

100

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“…In rabbits, the uptake of LPS by the adrenal glands was increased after LPS binding to HDL, which indicates that binding of LPS to HDL results in a decreased recognition by LPS receptors (347,372). Since then, in vivo and in vitro experiments have shown that LPS and LTA bind to and are neutralized by lipid emulsions (177,445), chylomicrons (194,195,447), VLDL (102,194,459,464,576), LDL (102,177,366,459,464,554,576), Lp(a) (385), HDL (102,144,177,374,459,464,535,576), ApoA-I (112, 135, 539), ApoB (112,464), and ApoE (449,555).…”

Section: Anti-inflammatory Rolementioning

confidence: 99%

“…Using a solidphase binding assay, they also observed that in the absence of LBP, LPS preferentially bound to LDL and VLDL. (375,464,535), to LDL and/or VLDL (102,554), or to all lipoproteins (102,459,554,562,576) depending on the lipid and/or protein distribution in the distinct lipoprotein fractions. A correlation between the cholesterol contents of the lipoprotein fractions and LPS association was proposed by Van Lenten et al (554), but with rHDL the neutralizing potency correlates with the phospholipid contents of the particle (72).…”

Section: Anti-inflammatory Rolementioning

confidence: 99%

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

2003

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Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins

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“…Delivery of LPS by LBP to macrophage receptors initiates signal transduction pathways that lead to the increased release of pro-inflammatory cytokines (34). On the other hand, the delivery of LPS to HDL by LBP results in the attenuation of the immune response to infection (35). HDL-bound LPS is redistributed to LDL and VLDL (36) and transported to liver.…”

Section: Macrophage Lipid Metabolism During Inflammationmentioning

confidence: 99%

Regulation of macrophage function in inflammation and atherosclerosis

Shibata

Glass

2009

Journal of Lipid Research

105

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Atherosclerosis can be considered as both a chronic inflammatory disease and a lipid metabolism disorder. Innate immunity pathways have long been suspected to contribute to the initiation and progression of atherosclerosis. This suggests that crosstalk between lipid metabolism and innate immunity pathways plays an important role for the development and/or the prevention of atherosclerosis. However, it is not fully defined how innate immunity affects lipid metabolism. Macrophages play a central role in atherogenesis through the accumulation of cholesterol and the production of inflammatory mediators and cytokines. Liver X receptors (LXRs) exert an important atheroprotective effect in the macrophage. In addition to regulating cholesterol metabolism, LXRs are also negative regulators of macrophage inflammatory gene responses. In this review, we will discuss the roles of LXRs in the macrophage as key factors that link innate immunity and lipid metabolism. Cardiovascular disease, including atherosclerosis, is the leading cause of morbidity and mortality in western societies. Atherosclerosis is a chronic inflammatory disease and a disorder of lipid metabolism. Although many epidemiological studies have shown that high concentrations of LDL cholesterol are a major risk factor for atherosclerosis, innate immunity pathways have long been suspected to contribute to the initiation and progression of atherosclerosis. Atherosclerotic lesion progression has been shown to depend on chronic inflammation in the artery wall (1). After induction of hyperlipidemia, a rapid influx of monocytes into the arterial intima occurs; if persistent, this influx generates the chronic inflammation characteristic of the atherosclerotic plaque (2). Many pro-inflammatory genes activated by pathogen engagement of innate immunity signaling pathways are also induced in macrophages present in atherosclerotic lesions.Macrophages play a central role in the atherogenic process as modulators of both lipid metabolism and immune responses (1, 3). The accumulation of cholesterol-loaded macrophages in the arterial wall is the hallmark of the early atherosclerotic lesion (4, 5). In response to lipid loading, macrophages activate a compensatory pathway for cholesterol efflux mediated by the ATP binding cassette transporters A1 and G1 (ABCA1 and ABCG1) (6, 7). In the face of systemic hypercholesterolemia, however, this homeostatic mechanism is overwhelmed, leading to the development of foam cells and the fatty streak lesion. In fact, combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice (8). Cholesterol loading of macrophages stimulates the production of inflammatory mediators, such as cytokines and reactive oxygen species that recruit other cell types and contribute to the development of a complex lesion (9). Thus, processes that interfere with the intracellular cholesterol balance would be expected to exacerbate lesion formation.Liver X receptors (LXRs) are ligand-activated transcription factor...

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Different binding of¹²⁵I-LPS to plasma proteins from persons with high or low HDL

Cited by 25 publications

References 30 publications

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Regulation of macrophage function in inflammation and atherosclerosis

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Different binding of125I-LPS to plasma proteins from persons with high or low HDL

Cited by 25 publications

References 30 publications

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction

Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

Regulation of macrophage function in inflammation and atherosclerosis

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Product

Resources

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Different binding of¹²⁵I-LPS to plasma proteins from persons with high or low HDL