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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.


Representative images of livers immunostained for Gr-1.WT (A–C); (A) Normal Saline (B) LPS at 200× magnification (C) LPS at 400× magnification. β2GPI−/− (D–F); (D) Normal Saline (E) LPS at 200× magnification (F) LPS at 400× magnification. Arrows indicate representative positive immunostaining for Gr-1 (brown staining). Quantitation of inflammatory cells staining for Gr-1 (granulocyte marker). (G) The number of anti-Gr-1 positive cells per 10 high power fields (HPF) at 400× magnification. Data represent mean ± SEM, n = 5 ***p < 0.001. Mann-Whitney test.
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f2: Representative images of livers immunostained for Gr-1.WT (A–C); (A) Normal Saline (B) LPS at 200× magnification (C) LPS at 400× magnification. β2GPI−/− (D–F); (D) Normal Saline (E) LPS at 200× magnification (F) LPS at 400× magnification. Arrows indicate representative positive immunostaining for Gr-1 (brown staining). Quantitation of inflammatory cells staining for Gr-1 (granulocyte marker). (G) The number of anti-Gr-1 positive cells per 10 high power fields (HPF) at 400× magnification. Data represent mean ± SEM, n = 5 ***p < 0.001. Mann-Whitney test.

Mentions: Liver tissue was obtained at 6 h following intravenous LPS administration. β2GPI−/− compared to WT mice demonstrated increased staining with anti-Gr-1 antibody (representative images of Gr-1 staining Fig. 2A–F) consistent with increased neutrophil infiltration into the liver (211.2 vs. 90.2 (positive cells/per 10 high power fields (HPF)), n = 5, p = 0.03) (Fig. 2G). No significant difference was detected in the number of apoptotic cells in the livers of the β2GPI−/− mice 6 h post LPS compared to WT at the identical time point. There was a significant increase in neutrophil infiltration in the β2GPI−/− compared to WT livers when mice were administered pyrogen free saline n = 5, p = 0.03 (Fig. 2G).


Gram Negative Bacterial Inflammation Ameliorated by the Plasma Protein Beta 2-Glycoprotein I
Representative images of livers immunostained for Gr-1.WT (A–C); (A) Normal Saline (B) LPS at 200× magnification (C) LPS at 400× magnification. β2GPI−/− (D–F); (D) Normal Saline (E) LPS at 200× magnification (F) LPS at 400× magnification. Arrows indicate representative positive immunostaining for Gr-1 (brown staining). Quantitation of inflammatory cells staining for Gr-1 (granulocyte marker). (G) The number of anti-Gr-1 positive cells per 10 high power fields (HPF) at 400× magnification. Data represent mean ± SEM, n = 5 ***p < 0.001. Mann-Whitney test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037396&req=5

f2: Representative images of livers immunostained for Gr-1.WT (A–C); (A) Normal Saline (B) LPS at 200× magnification (C) LPS at 400× magnification. β2GPI−/− (D–F); (D) Normal Saline (E) LPS at 200× magnification (F) LPS at 400× magnification. Arrows indicate representative positive immunostaining for Gr-1 (brown staining). Quantitation of inflammatory cells staining for Gr-1 (granulocyte marker). (G) The number of anti-Gr-1 positive cells per 10 high power fields (HPF) at 400× magnification. Data represent mean ± SEM, n = 5 ***p < 0.001. Mann-Whitney test.
Mentions: Liver tissue was obtained at 6 h following intravenous LPS administration. β2GPI−/− compared to WT mice demonstrated increased staining with anti-Gr-1 antibody (representative images of Gr-1 staining Fig. 2A–F) consistent with increased neutrophil infiltration into the liver (211.2 vs. 90.2 (positive cells/per 10 high power fields (HPF)), n = 5, p = 0.03) (Fig. 2G). No significant difference was detected in the number of apoptotic cells in the livers of the β2GPI−/− mice 6 h post LPS compared to WT at the identical time point. There was a significant increase in neutrophil infiltration in the β2GPI−/− compared to WT livers when mice were administered pyrogen free saline n = 5, p = 0.03 (Fig. 2G).

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.