Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner

Inflammation. 2016 Oct;39(5):1737-46. doi: 10.1007/s10753-016-0408-1.

Abstract

Endothelial activation with excessive recruitment and adhesion of immune cells plays a central role in the progression of sepsis. We established a microfluidic system to study the activation of human umbilical vein endothelial cells by conditioned medium containing plasma from lipopolysaccharide-stimulated whole blood or from septic blood and to investigate the effect of adsorption of inflammatory mediators on endothelial activation. Treatment of stimulated whole blood with polystyrene-divinylbenzene-based cytokine adsorbents (average pore sizes 15 or 30 nm) prior to passage over the endothelial layer resulted in significantly reduced endothelial cytokine and chemokine release, plasminogen activator inhibitor-1 secretion, adhesion molecule expression, and in diminished monocyte adhesion. Plasma samples from sepsis patients differed substantially in their potential to induce endothelial activation and monocyte adhesion despite their almost identical interleukin-6 and tumor necrosis factor-alpha levels. Pre-incubation of the plasma samples with a polystyrene-divinylbenzene-based adsorbent (30 nm average pore size) reduced endothelial intercellular adhesion molecule-1 expression to baseline levels, resulting in significantly diminished monocyte adhesion. Our data support the potential of porous polystyrene-divinylbenzene-based adsorbents to reduce endothelial activation under septic conditions by depletion of a broad range of inflammatory mediators.

Keywords: cytokine adsorption; endothelium; lipopolysaccharide; monocyte adhesion; sepsis.

MeSH terms

  • Adsorption
  • Cell Adhesion*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism
  • Human Umbilical Vein Endothelial Cells / immunology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Monocytes / cytology*
  • Polystyrenes / therapeutic use*
  • Porosity
  • Sepsis / immunology*
  • Sepsis / therapy
  • Vinyl Compounds / therapeutic use*

Substances

  • Inflammation Mediators
  • Polystyrenes
  • Vinyl Compounds
  • divinyl benzene