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

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 (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.


(A–G) β2GPI deficient mice had a significant increase in plasma inflammatory cytokines at 2 h and 6 h time points following LPS challenge. (A) TNFα at 2 h (B) TNFα at 6 h. For IL-6, IFNγ, MIP-1α, MIP-1β and Eotaxin (C–G) at 6 h. (□) = WT = Wild Type mice, (■) = β2GPI−/− = β2-glycoprotein I deficient mice. Mann-Whitney test n = 5 *p < 0.05, **p < 0.01, ***p < 0.001.
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f1: (A–G) β2GPI deficient mice had a significant increase in plasma inflammatory cytokines at 2 h and 6 h time points following LPS challenge. (A) TNFα at 2 h (B) TNFα at 6 h. For IL-6, IFNγ, MIP-1α, MIP-1β and Eotaxin (C–G) at 6 h. (□) = WT = Wild Type mice, (■) = β2GPI−/− = β2-glycoprotein I deficient mice. Mann-Whitney test n = 5 *p < 0.05, **p < 0.01, ***p < 0.001.

Mentions: Significantly higher levels of TNFα were noted at both 2 and 6 h post LPS injection in the β2GPI−/− mice compared to the WT mice (Fig. 1A,B). Significantly higher levels of IL-6, IFN-γ, MIP-1α,β and Eotaxin-1 (Fig. 1C–G) were detected in the β2GPI−/− compared to WT mice 6 h post intravenous LPS administration.


Gram Negative Bacterial Inflammation Ameliorated by the Plasma Protein Beta 2-Glycoprotein I
(A–G) β2GPI deficient mice had a significant increase in plasma inflammatory cytokines at 2 h and 6 h time points following LPS challenge. (A) TNFα at 2 h (B) TNFα at 6 h. For IL-6, IFNγ, MIP-1α, MIP-1β and Eotaxin (C–G) at 6 h. (□) = WT = Wild Type mice, (■) = β2GPI−/− = β2-glycoprotein I deficient mice. Mann-Whitney test n = 5 *p < 0.05, **p < 0.01, ***p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037396&req=5

f1: (A–G) β2GPI deficient mice had a significant increase in plasma inflammatory cytokines at 2 h and 6 h time points following LPS challenge. (A) TNFα at 2 h (B) TNFα at 6 h. For IL-6, IFNγ, MIP-1α, MIP-1β and Eotaxin (C–G) at 6 h. (□) = WT = Wild Type mice, (■) = β2GPI−/− = β2-glycoprotein I deficient mice. Mann-Whitney test n = 5 *p < 0.05, **p < 0.01, ***p < 0.001.
Mentions: Significantly higher levels of TNFα were noted at both 2 and 6 h post LPS injection in the β2GPI−/− mice compared to the WT mice (Fig. 1A,B). Significantly higher levels of IL-6, IFN-γ, MIP-1α,β and Eotaxin-1 (Fig. 1C–G) were detected in the β2GPI−/− compared to WT mice 6 h post intravenous LPS administration.

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.