Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats

Read, Thomas E.; Grünfeld, Carl; Kumwenda, Zindaba L.; Calhoun, M C; Kane, John P.; Feingold, Kenneth R.; Rapp, Joseph H.

doi:10.1016/s0039-6060(05)80231-4

Cited by 56 publications

(44 citation statements)

References 31 publications

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“…Infusion of reconstituted HDL protects against endotoxic shock and gram-negative bacteremia in rabbits (309)(310)(311). Improved survival occurs when infusions of chylomicron or synthetic TG-rich lipid emulsion were given to animals up to 30 min after LPS, indicating that lipoproteins may have a therapeutic role during endotoxemia (312). Additionally, TG-rich lipoproteins protect rats from death when gram-negative sepsis is induced by cecal ligation and puncture (313).…”

Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

“…Although cytokines play a role in host defense, high levels of cytokine secretion are the cause of septic shock. However, binding of LPS by lipoproteins decreased uptake by hepatic macrophages and increased uptake by hepatocytes, resulting in rapid secretion of LPS into the bile (308,312,321). Consistent with these findings, circulating levels of TNF were lower (308).…”

Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

“…Furthermore, conflicting evidence exists regarding the necessary component(s) of lipoproteins (lipid vs. protein) that attenuates the toxic effects of LPS. Lipid emulsions, which are devoid of proteins, demonstrate LPS-neutralizing effects similar to those of TG-rich lipoproteins, suggesting that the protein component of the lipoproteins may not be necessary (295,312,313). Ultrastructural studies of the LPS-LDL complex also show that the fatty acyl chain of the toxic lipid A moiety of LPS is inserted into the phospholipid surface of lipoproteins, thus masking the active site of LPS (329).…”

Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

See 2 more Smart Citations

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Khovidhunkit

Kim

Memon

et al. 2004

Journal of Lipid Research

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Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

Section: Lipoproteins and Bacterial Endotoxinmentioning

confidence: 99%

See 1 more Smart Citation

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Khovidhunkit

Kim

Memon

et al. 2004

Journal of Lipid Research

Self Cite

1,306

1,200

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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%

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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“…[3][4][5][6] The protective capacity of lipoproteins is associated with the increased clearance of circulating LPS by the liver and the re-direction of the toxic macromolecule from Kupffer cells to hepatocytes. 7,8 While the capacity of TG-rich lipoproteins to bind and neutralize LPS can be accurately predicted by the phospholipid content of the lipid particles, additional protein constituents of the lipid particle also play an important role in the process.…”

Section: Introductionmentioning

confidence: 99%

Lipoprotein-bound LPS induces cytokine tolerance in hepatocytes

Harris

Kasravi

2003

Journal of Endotoxin Research

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Bacterial endotoxin (LPS) elicits dramatic responses in the host including elevated plasma lipid levels due to the increased synthesis and secretion of triglyceride (TG)-rich lipoproteins by the liver. We postulate that this cytokine-induced hyperlipoproteinemia, clinically termed the `lipemia of sepsis', represents an innate, non-adaptive host immune response to infection. Data in support of this hypothesis include the capacity of TG-rich lipoproteins (VLDL and chylomicrons, CM) to bind and neutralize LPS. Herein, we present evidence that CM-bound LPS attenuates the hepatocellular response to pro-inflammatory cytokines. Primary rodent hepatocytes pretreated with CM—LPS complexes for 2 h demonstrated a near 70% reduction in cytokine-induced NO production as compared to non-pretreated control cells ( P ≥ 0.04). Whereas hepatocytes were maximally tolerant to cytokine stimulation 6 h after CM—LPS pretreatment, the cells spontaneously regained cytokine responsiveness within 40 h. The induction of cytokine tolerance in hepatocytes follows the internalization of CM—LPS complexes and is a process regulated by the LDL receptor. CM—LPS complexes failed to induce cytokine tolerance in hepatocytes wherein lipoprotein receptor activity was inhibited with high dose receptor associated protein (30 μg/ml). Similarly, CM-bound LPS did not induce tolerance in hepatocytes from ldlr—/— mice. Thus, the biochemical or genetic inhibition of LDL receptor activity effectively prevented the CM-mediated induction of the cytokine tolerant phenotype. In conclusion, the lipemia of sepsis likely represents a mechanism by which the host combats sporadic, non-life-threatening episodes of endotoxemia. Also, it may indicate a negative regulatory mechanism for the hepatic response to sepsis, serving to effectively down-regulate the acute phase response. A better understanding of how TG-rich lipoproteins modulate the host response to LPS could yield novel biological insights with important clinical implications, including the development of lipid-based therapies for bacterial infections.

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Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats

Cited by 56 publications

References 31 publications

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host

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

Lipoprotein-bound LPS induces cytokine tolerance in hepatocytes

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