Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions
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ORIGINAL ARTICLE
Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner Tanja Eichhorn,1 Sabine Rauscher,2 Caroline Hammer,1,2 Marion Gröger,2 Michael B. Fischer,1,3 and Viktoria Weber1,4
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 polystyrenedivinylbenzene-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. KEY WORDS: cytokine adsorption; endothelium; sepsis; lipopolysaccharide; monocyte adhesion.
INTRODUCTION As a barrier between the blood stream and the surrounding tissues, the endothelium orchestrates tissue homeostasis, angiogenesis, and hemostasis; contributes to innate immunity; and plays a major role in regulating the physiological as well as the pathological host response to infection [1, 2]. In systemic infection, activation of the endothelium by pathogen-associated molecular patterns or by host-derived mediators such as chemokines, cytokines, and complement factors induces a shift of the endothelial surface towards a pro-coagulant and adhesive state. Excessive recruitment and adhesion of immune cells trigger sustained endothelial activation, increased vascular permeability, and impaired microcirculation, which are centrally involved in a variety of inflammatory conditions including sepsis and sepsis-associated multiple organ failure [3, 4].
Michael B. Fischer and Viktoria Weber contributed equally to this work. Electronic supplementary material The online version of this article (doi:10.1007/s10753-016-0408-1) contains supplementary material, which is available to authorized users. 1
Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Department for He
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