beta(2)-Glycoprotein I: a novel component of innate immunity

Sepsis is a systemic host response to invasive infection by bacteria. Despite treatment with antibiotics, current mortality rates are in the range of 20%-25%, which makes sepsis the most important cause of death in intensive care. Gram-negative bacteria are a prominent cause of sepsis. Lipopolysaccharide (LPS), one of the major constituents of the outer membrane of Gram-negative bacteria, plays a major role in activating the host's immune response by binding to monocytes and other cells. Several proteins are involved in neutralization and clearance of LPS from the bloodstream. Here, we provide evidence that beta(2)-glycoprotein I (beta(2)GPI) is a scavenger of LPS. In vitro, beta(2)GPI inhibited LPS-induced expression of tissue factor and IL-6 from monocytes and endothelial cells. Binding of beta(2)GPI to LPS caused a conformational change in beta(2)GPI that led to binding of the beta(2)GPI-LPS complex to monocytes and ultimately clearance of this complex. Furthermore, plasma levels of beta(2)GPI were inversely correlated with temperature rise and the response of inflammatory markers after a bolus injection of LPS in healthy individuals. Together, these observations provide evidence that beta(2)GPI is involved in the neutralization and clearance of LPS and identify beta(2)GPI as a component of innate immunity. (Blood. 2011;117(25):6939-6947)

de Groot, Philip G. (author)
Mörgelin, MatthiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-mmn (author)
Monk, Stephanie D. D. C. (author)
van Os, Gwendolyn (author)
Levels, Johannes H. M. (author)
de Laat, Bas (author)
Urbanus, Rolf T. (author)
Herwald, HeikoLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)medk-hhe (author)
van der Poll, Tom (author)
Meijers, Joost C. M. (author)
InfektionsmedicinSektion III (creator_code:org_t)

By the author/editor: Agar, Cetin; de Groot, Philip ...; Mörgelin, Matthi ...; Monk, Stephanie ...; van Os, Gwendoly ...; Levels, Johannes ...; show more...; de Laat, Bas; Urbanus, Rolf T.; Herwald, Heiko; van der Poll, To ...; Meijers, Joost C ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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