β2-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. Lipopolysacch...

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Bibliographic Details
Published in:Blood 2011-06, Vol.117 (25), p.6939-6947
Main Authors: Ağar, Çetin, de Groot, Philip G., Mörgelin, Matthias, Monk, Stephanie D.D.C., van Os, Gwendolyn, Levels, Johannes H.M., de Laat, Bas, Urbanus, Rolf T., Herwald, Heiko, van der Poll, Tom, Meijers, Joost C.M.
Format: Article
Language:English
Subjects:
beta 2-Glycoprotein I - blood
beta 2-Glycoprotein I - immunology
Biological and medical sciences
Cell Line
Cells, Cultured
Endothelial Cells - immunology
Escherichia coli - immunology
Hematologic and hematopoietic diseases
Humans
Immunity, Innate
Interleukin-6 - immunology
Lipopolysaccharides - immunology
Medical sciences
Monocytes - immunology
Sepsis - immunology
Thromboplastin - immunology
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Summary: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 β2-glycoprotein I (β2GPI) is a scavenger of LPS. In vitro, β2GPI inhibited LPS-induced expression of tissue factor and IL-6 from monocytes and endothelial cells. Binding of β2GPI to LPS caused a conformational change in β2GPI that led to binding of the β2GPI-LPS complex to monocytes and ultimately clearance of this complex. Furthermore, plasma levels of β2GPI 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 β2GPI is involved in the neutralization and clearance of LPS and identify β2GPI as a component of innate immunity.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2010-12-325951