Title
Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in gram-negative sepsis.
Author
Berbée, J.F.
van der Hoogt, C.C.
Kleemann, R.
Schippers, E.F.
Kitchens, R.L.
van Dissel, J.T.
Bakker-Woudenberg, I.A.
Havekes, L.M.
Rensen, P.C.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
Gram-negative sepsis is a major death cause in intensive care units. Accumulating evidence indicates the protective role of plasma lipoproteins such as high-density lipoprotein (HDL) in sepsis. It has recently been shown that septic HDL is almost depleted from apolipoprotein CI (apoCI), suggesting that apoCI may be a protective factor in sepsis. Sequence analysis revealed that apoCI possesses a highly conserved consensus KVKEKLK binding motif for lipopolysaccharide (LPS), an outer-membrane component of gram-negative bacteria. Through avid binding to LPS involving this motif, apoCI improved the presentation of LPS to macrophages in vitro and in mice, thereby stimulating the inflammatory response to LPS. Moreover, apoCI dose-dependently increased the early inflammatory response to Klebsiella pneumoniae-induced pneumonia, reduced the number of circulating bacteria, and protected mice against fatal sepsis. Our data support the hypothesis that apoCI is a physiological protector against infection by enhancing the early inflammatory response to LPS and suggest that timely increase of apoCI levels could be used to efficiently prevent and treat early sepsis. Chemicals / CAS: Apolipoprotein C-I; Apolipoproteins C; Lipopolysaccharides
Subject
Biology
Drug effect
Gram negative bacterium
Immunology
Mortality
Mouse
Mouse mutant
Nucleotide sequence
Transgenic mouse
Animals
Antigen Presentation
Apolipoprotein C-I
Apolipoproteins C
Binding Sites
Conserved Sequence
Gram-Negative Bacteria
Humans
Immunity
Inflammation
Lipopolysaccharides
Macrophages
Mice
Mice, Knockout
Mice, Transgenic
Sepsis
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http://resolver.tudelft.nl/uuid:72adbcad-a047-4039-aeb6-90904f6f883e
TNO identifier
239513
ISSN
1530-6860
Source
The FASEB journal, 20 (12), 2162-2164
Document type
article