title: β₂-glycoprotein I: a novel component of innate immunity.
abstract: 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.
authors: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Cetin
authors: C
authors: Agar
authors: Philip G
authors: PG
authors: de Groot
authors: Matthias
authors: M
authors: Mörgelin
authors: Stephanie D D C
authors: SD
authors: Monk
authors: Gwendolyn
authors: G
authors: van Os
authors: Johannes H M
authors: JH
authors: Levels
authors: Bas
authors: B
authors: de Laat
authors: Rolf T
authors: RT
authors: Urbanus
authors: Heiko
authors: H
authors: Herwald
authors: Tom
authors: T
authors: van der Poll
authors: Joost C M
authors: JC
authors: Meijers
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D018805:Sepsis / Q000276:immunology; D013925:Thromboplastin / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000097:blood / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin