Scientific article

Increased release of sMD-2 during human endotoxemia and sepsis: a role for endothelial cells

Published inMolecular immunology, vol. 45, no. 11, p. 3268-3277
Publication date2008

MD-2 is the crucial cofactor of TLR4 in the detection of LPS. Here, we show that soluble MD-2 (sMD-2) circulates in plasma of healthy individuals as a polymeric protein. The total amount of sMD-2 in septic plasma was strongly elevated and contained both sMD-2 polymers and monomers, the latter representing the putative biologically active form of MD-2. Moreover, during experimental human endotoxemia, the monomeric and total sMD-2 content in plasma increased with the kinetics of an acute phase protein. The increase in sMD-2 monomers was paralleled by enhanced TLR4 costimulatory activity. The presence of functional sMD-2 during endotoxemia and sepsis was confirmed by immunodepletion. Immunohistochemistry revealed that MD-2 expression in septic patients was strongly enhanced on endothelium and multiple inflammatory cells in lung and liver. In vitro studies showed that sMD-2 release appears to be restricted to endothelial cells and dendritic cells. Release of sMD-2 by endothelial cells was strongly enhanced by LPS and TNF-alpha stimulation. Taken together, this study demonstrates the increase of both circulating polymeric and functional monomeric sMD-2 during endotoxemia and sepsis, and evidence is provided that the endothelium is involved in this process.

  • Adult
  • Case-Control Studies
  • Endothelial Cells/drug effects/immunology/metabolism/pathology
  • Endotoxemia/immunology/metabolism
  • Female
  • Hematopoietic System/cytology/drug effects
  • Humans
  • Kinetics
  • Lipopolysaccharides/pharmacology
  • Liver/drug effects/immunology/pathology
  • Lung/drug effects/immunology/pathology
  • Lymphocyte Antigen 96/blood/secretion
  • Male
  • Middle Aged
  • Sepsis/blood/immunology/metabolism
  • Solubility/drug effects
  • Tumor Necrosis Factor-alpha/pharmacology
Citation (ISO format)
WOLFS, Tim G.A.M. et al. Increased release of sMD-2 during human endotoxemia and sepsis: a role for endothelial cells. In: Molecular immunology, 2008, vol. 45, n° 11, p. 3268–3277. doi: 10.1016/j.molimm.2008.02.014
Main files (1)
Article (Accepted version)
ISSN of the journal0161-5890

Technical informations

Creation06/26/2009 2:56:00 PM
First validation06/26/2009 2:56:00 PM
Update time03/14/2023 3:09:25 PM
Status update03/14/2023 3:09:25 PM
Last indexation10/17/2023 2:42:10 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack