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

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.