Journal
BLOOD
Volume 117, Issue 25, Pages 6939-6947Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-325951
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Funding
- Swedish Medical Research Council [2008-7480]
- Foundations of Crafoord
- Greta och Johan Kock's stiftelser
- Alfred Osterlund's stiftelse
- Konung Gustav V's 80-Arsfond
- Swedish Society for Medicine
- Medical Faculty, Lund University
- Netherlands Organization for Scientific Research (ZonMW)
- Academic Medical Center
- Netherlands Heart Foundation [2006T053]
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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)
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