beta(2)-Glycoprotein I: a novel component of innate immunity
Agar, Cetin ; de Groot, Philip G. ; Mörgelin, Matthias LU ; Monk, Stephanie D. D. C. ; van Os, Gwendolyn ; Levels, Johannes H. M. ; de Laat, Bas ; Urbanus, Rolf T. ; Herwald, Heiko LU
and van der Poll, Tom
, et al.
(2011)
In Blood
117(25).
p.6939-6947
- 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 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... (More)
- 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) (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2049247
- author
- Agar, Cetin
; de Groot, Philip G.
; Mörgelin, Matthias
LU
; Monk, Stephanie D. D. C.
; van Os, Gwendolyn
; Levels, Johannes H. M.
; de Laat, Bas
; Urbanus, Rolf T.
; Herwald, Heiko
LU
and van der Poll, Tom
, et al. (More)
- Agar, Cetin
; de Groot, Philip G.
; Mörgelin, Matthias
LU
; Monk, Stephanie D. D. C.
; van Os, Gwendolyn
; Levels, Johannes H. M.
; de Laat, Bas
; Urbanus, Rolf T.
; Herwald, Heiko
LU
; van der Poll, Tom
and Meijers, Joost C. M.
(Less)
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 117
- issue
- 25
- pages
- 6939 - 6947
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000291979800026
- scopus:79959532387
- pmid:21454452
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2010-12-325951
- language
- English
- LU publication?
- yes
- id
- 3443f7fe-fbf4-473b-b51d-a7cc36c6eb0b (old id 2049247)
- date added to LUP
- 2016-04-01 10:45:34
- date last changed
- 2022-04-28 01:12:15
@article{3443f7fe-fbf4-473b-b51d-a7cc36c6eb0b,
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 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)}},
author = {{Agar, Cetin and de Groot, Philip G. and Mörgelin, Matthias and Monk, Stephanie D. D. C. and van Os, Gwendolyn and Levels, Johannes H. M. and de Laat, Bas and Urbanus, Rolf T. and Herwald, Heiko and van der Poll, Tom and Meijers, Joost C. M.}},
issn = {{1528-0020}},
language = {{eng}},
number = {{25}},
pages = {{6939--6947}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{beta(2)-Glycoprotein I: a novel component of innate immunity}},
url = {{http://dx.doi.org/10.1182/blood-2010-12-325951}},
doi = {{10.1182/blood-2010-12-325951}},
volume = {{117}},
year = {{2011}},
}