title: Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner.
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.
authors: Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.
authors: Tanja
authors: T
authors: Eichhorn
authors: Core Facility Imaging, Medical University of Vienna, Vienna, Austria.
authors: Sabine
authors: S
authors: Rauscher
authors: Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.|Core Facility Imaging, Medical University of Vienna, Vienna, Austria.
authors: Caroline
authors: C
authors: Hammer
authors: Core Facility Imaging, Medical University of Vienna, Vienna, Austria.
authors: Marion
authors: M
authors: Gröger
authors: Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.|Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors: Michael B
authors: MB
authors: Fischer
authors: Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria. viktoria.weber@donau-uni.ac.at.
authors: Viktoria
authors: V
authors: Weber
mesh_terms: D000327:Adsorption; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011137:Polystyrenes / Q000627:therapeutic use*; D016062:Porosity; D018805:Sepsis / Q000276:immunology* / Q000628:therapy; D014753:Vinyl Compounds / Q000627:therapeutic use*
chemical_list: D018836:Inflammation Mediators; D011137:Polystyrenes; D014753:Vinyl Compounds; C004985:divinyl benzene
keywords: cytokine adsorption; endothelium; lipopolysaccharide; monocyte adhesion; sepsis