Reconstituted high-density lipoprotein modulates activation of human leukocytes

PLoS One. 2013 Aug 14;8(8):e71235. doi: 10.1371/journal.pone.0071235. eCollection 2013.

Abstract

An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC). Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA)-induced secretion of the cytokines IL-1β, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40), IL-15 and IFN-α was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2)- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-κB. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-2 Antigen / metabolism
  • Chemokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dose-Response Relationship, Drug
  • Granulocytes / drug effects
  • Granulocytes / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Kinetics
  • Leukocytes / drug effects*
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Lipoproteins, HDL / pharmacology*
  • Monocytes / cytology
  • NF-kappa B / metabolism
  • Toll-Like Receptor 2 / metabolism
  • Up-Regulation / drug effects

Substances

  • B7-2 Antigen
  • Chemokines
  • Lipopolysaccharide Receptors
  • Lipoproteins, HDL
  • NF-kappa B
  • Toll-Like Receptor 2
  • Intercellular Adhesion Molecule-1

Grants and funding

This work was supported by the EU 6th Framework Integrated Research Project “Reprogramming the Immune System for the Establishment of Tolerance” (RISET) and the Swiss National Science Foundation (grants no. 3200B0-116618 and 32003B_135272). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.