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Gram Negative Bacterial Inflammation Ameliorated by the Plasma Protein Beta 2-Glycoprotein I

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ABSTRACT

Lipopolysaccharide (LPS) is a major component of the outer wall of gram negative bacteria. In high doses LPS contributes to the inflammation in gram negative sepsis, and in low doses contributes to the low grade inflammation characteristic of the metabolic syndrome. We wanted to assess the role of beta2-glycoprotein I (β2GPI) a highly conserved plasma protein and its different biochemical forms in a mouse model of LPS systemic inflammation. Normal and β2GPI deficient mice were administered LPS through their veins and assessed for a range of inflammation markers in their blood and liver. Different biochemical forms of β2GPI were measured in normal mice given either saline or LPS. We show that β2GPI has a significant role in inhibiting LPS induced inflammation. In this study we provide some evidence that β2GPI serves a protective role in a mouse model of LPS inflammation. This resolves the controversy of previous studies which used LPS and β2GPI in test tube based models of LPS induced activation of white cells. We also highlight the potential relevance of a newly discovered biochemical form of β2GPI in LPS mediated inflammation and we speculate that this form has a protective role against LPS induced pathology.

No MeSH data available.


Related in: MedlinePlus

LPS but not Lipid A increases free thiol generation in β2GPI in the presence of TRX-1.Free thiol β2GPI generation increased only when β2GPI was incubated with LPS, but not Lipid A or PBS in the presence of reduced thioredoxin-1 (TRX-1). There was no free thiol β2GPI generation when β2GPI was incubated with LPS or PBS in the absence of TRX-1. Data are mean ± SEM, n = 3 **p = <0.01. One Way ANOVA with Tukey’s multiple comparison test.
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f5: LPS but not Lipid A increases free thiol generation in β2GPI in the presence of TRX-1.Free thiol β2GPI generation increased only when β2GPI was incubated with LPS, but not Lipid A or PBS in the presence of reduced thioredoxin-1 (TRX-1). There was no free thiol β2GPI generation when β2GPI was incubated with LPS or PBS in the absence of TRX-1. Data are mean ± SEM, n = 3 **p = <0.01. One Way ANOVA with Tukey’s multiple comparison test.

Mentions: In view of the increase in the percentage of free thiol β2GPI demonstrated in the serum of LPS treated mice compared to the decrease in total β2GPI levels, we assessed the in-vitro effect of LPS on TRX-1 induced free thiols in β2GPI. LPS but not lipid A at equivalent concentrations significantly increased free thiols in β2GPI (Fig. 5). There was no free thiol β2GPI generation when β2GPI was incubated alone or with LPS in the absence of TRX-1.


Gram Negative Bacterial Inflammation Ameliorated by the Plasma Protein Beta 2-Glycoprotein I
LPS but not Lipid A increases free thiol generation in β2GPI in the presence of TRX-1.Free thiol β2GPI generation increased only when β2GPI was incubated with LPS, but not Lipid A or PBS in the presence of reduced thioredoxin-1 (TRX-1). There was no free thiol β2GPI generation when β2GPI was incubated with LPS or PBS in the absence of TRX-1. Data are mean ± SEM, n = 3 **p = <0.01. One Way ANOVA with Tukey’s multiple comparison test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC5037396&req=5

f5: LPS but not Lipid A increases free thiol generation in β2GPI in the presence of TRX-1.Free thiol β2GPI generation increased only when β2GPI was incubated with LPS, but not Lipid A or PBS in the presence of reduced thioredoxin-1 (TRX-1). There was no free thiol β2GPI generation when β2GPI was incubated with LPS or PBS in the absence of TRX-1. Data are mean ± SEM, n = 3 **p = <0.01. One Way ANOVA with Tukey’s multiple comparison test.
Mentions: In view of the increase in the percentage of free thiol β2GPI demonstrated in the serum of LPS treated mice compared to the decrease in total β2GPI levels, we assessed the in-vitro effect of LPS on TRX-1 induced free thiols in β2GPI. LPS but not lipid A at equivalent concentrations significantly increased free thiols in β2GPI (Fig. 5). There was no free thiol β2GPI generation when β2GPI was incubated alone or with LPS in the absence of TRX-1.

View Article: PubMed Central - PubMed

ABSTRACT

Lipopolysaccharide (LPS) is a major component of the outer wall of gram negative bacteria. In high doses LPS contributes to the inflammation in gram negative sepsis, and in low doses contributes to the low grade inflammation characteristic of the metabolic syndrome. We wanted to assess the role of beta2-glycoprotein I (&beta;2GPI) a highly conserved plasma protein and its different biochemical forms in a mouse model of LPS systemic inflammation. Normal and &beta;2GPI deficient mice were administered LPS through their veins and assessed for a range of inflammation markers in their blood and liver. Different biochemical forms of &beta;2GPI were measured in normal mice given either saline or LPS. We show that &beta;2GPI has a significant role in inhibiting LPS induced inflammation. In this study we provide some evidence that &beta;2GPI serves a protective role in a mouse model of LPS inflammation. This resolves the controversy of previous studies which used LPS and &beta;2GPI in test tube based models of LPS induced activation of white cells. We also highlight the potential relevance of a newly discovered biochemical form of &beta;2GPI in LPS mediated inflammation and we speculate that this form has a protective role against LPS induced pathology.

No MeSH data available.


Related in: MedlinePlus