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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2004-12-6
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pubmed:abstractText |
In this paper, we show that plasma from patients with severe sepsis and septic shock but not normal plasma supports lipopolysaccharide (LPS) activation of epithelial cells expressing Toll-like receptor 4 (TLR4). Recombinant soluble myeloid differentiation protein-2 (MD-2) complemented normal plasma and allowed LPS activation of epithelial cells to levels measured with "septic" plasma, whereas soluble MD-2-depleted plasma lost its effects. The same "MD-2 activity" was found in urine from a patient with septic shock and in lung edema fluids from patients with adult respiratory distress syndrome (ARDS). Recombinant soluble MD-2 enabled LPS-dependent activation of epithelial cells bearing TLR4. LPS-binding protein (LBP) and soluble CD14 increased the sensitivity of TLR4-expressing epithelial cells to LPS but were not able to mediate LPS activation of these cells in the absence of soluble MD-2. An anti-MD-2 monoclonal antibody blocked LPS activation of TLR4-expressing cells only in the presence of septic plasma or septic urine. These results suggest that septic plasma containing soluble MD-2 leaking into the extravascular space supports LPS activation of TLR4-expressing epithelial cells. We therefore propose that soluble MD-2 is an important mediator of organ inflammation during sepsis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/LY96 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Antigen 96,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TLR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4071-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15328161-Antigens, Surface,
pubmed-meshheading:15328161-Carrier Proteins,
pubmed-meshheading:15328161-Cell Line,
pubmed-meshheading:15328161-DNA Primers,
pubmed-meshheading:15328161-Endothelium, Vascular,
pubmed-meshheading:15328161-Humans,
pubmed-meshheading:15328161-Inflammation,
pubmed-meshheading:15328161-Kidney,
pubmed-meshheading:15328161-Lipopolysaccharides,
pubmed-meshheading:15328161-Lymphocyte Antigen 96,
pubmed-meshheading:15328161-Membrane Glycoproteins,
pubmed-meshheading:15328161-Polymerase Chain Reaction,
pubmed-meshheading:15328161-Receptors, Cell Surface,
pubmed-meshheading:15328161-Recombinant Fusion Proteins,
pubmed-meshheading:15328161-Sepsis,
pubmed-meshheading:15328161-Shock, Septic,
pubmed-meshheading:15328161-Toll-Like Receptor 4,
pubmed-meshheading:15328161-Toll-Like Receptors
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pubmed:year |
2004
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pubmed:articleTitle |
Soluble MD-2 activity in plasma from patients with severe sepsis and septic shock.
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pubmed:affiliation |
Laboratory of the Division of Intensive Care, Department of Internal Medicine, University Hospital of Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. jerome.pugin@medecine.unige.ch
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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