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Einfluss verminderter Scherkräfte auf Entzündungsreaktionen in vitro

Effekte pathologischer Strömungsbedingungen auf Leukozyten-Endothel-Interaktionen und monozytäre „Tissue-factor-Expression“ in humanen Zellkulturen

Effects of reduced shear stress on inflammatory reactions in vitro

Effects of pathological flow conditions on leukocyte-endothelial interactions and monocyte tissue factor expression in human cell cultures

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Zusammenfassung

Hintergrund

Leukozyten-Endothel-Interaktionen stellen ein wichtiges Bindeglied zwischen Perfusionsstörungen und Entzündungsreaktionen dar. Die vorliegende Untersuchung sollte die Frage beantworten, welchen Anteil reduzierte Scherkräfte an Leukozyten-Endothel-Interaktionen besitzen, und ob durch hydrodynamische Störungen direkt Entzündungsreaktionen, wie die Induktion von „tissue factor“ (TF) ausgelöst werden können.

Methoden

Aktivierte und nichtaktivierte humane Endothelzellen aus Nabelschnurvenen wurden bei einer Schubspannung von 0–3 dyn/cm2 mit neutrophilen Granulozyten und Monozyten in einer Flusskammer koinkubiert. Ausgewertet wurden die Leukozytenadhäsion und die darauf folgende TF-Expression auf adhärenten Monozyten.

Ergebnisse

Bei 2–3 dyn/cm2 wurde eine relevante Adhäsion nur auf Tumor-Nekrose-Faktor- (TNF-)α-aktiviertem Endothel beobachtet. Unter 1 dyn/cm2 stieg die Adhäsion jedoch auch auf nichtaktiviertem Endothel steil an. Jene strömungsbedingte Adhäsion wurde von einer Steigerung der TF-Expression begleitet, die sich unter statischen Bedingungen nicht mehr zwischen aktivierten und nichtaktivierten Kokulturen unterschied.

Schlussfolgerung

Verminderte Scherkräfte scheinen auch ohne weitere Trigger direkt Entzündungsreaktionen auslösen zu können.

Abstract

Background

During malperfusion and inflammation leukocyte adhesion is common. The purpose of this study was to examine the effects of reduced shear stress on leukocyte-endothelial interactions and subsequent inflammatory reactions such as up-regulation of tissue factor.

Methods

Isolated neutrophils and monocytes were co-incubated with human umbilical venous endothelium at 0–3 dynes/cm2 in a flow chamber. Adhesion and tissue factor expression on adherent leukocytes were examined at various flow conditions.

Results

At 2–3 dynes/cm2 adhesion occurred only on TNFα-activated endothelium. Below 1 dyne/cm2 similarly increased adhesion was also observed on non-activated endothelium. As was observed for leukocyte adhesion, these shear stress-dependent cell interactions also resulted in an up-regulation of tissue factor on adherent monocytes from non-activated co-cultures.

Conclusion

Apart from additional activators of inflammation, reduced shear forces may directly contribute to inflammation.

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Authors and Affiliations

  1. Abteilung für Anaesthesiologie und Intensivmedizin, Universitätsklinikum, Tübingen

    B. Nohé, T. Johannes, T. H. Schroeder, R. T. Kiefer, K. Unertl & H. J. Dieterich

  2. Department of Physiology, Academic Medical Center, University, , Amsterdam, Niederlande

    T. Johannes

  3. II. Chirurgische Klinik, Klinikum, Augsburg

    V. Schmidt

  4. Abteilung für Anaesthesiologie und Intensivmedizin, Universitätsklinikum, Hoppe-Seyler-Str. 3, 72076, Tübingen

    B. Nohé

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  1. B. Nohé
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  4. T. H. Schroeder
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  5. R. T. Kiefer
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Correspondence to B. Nohé.

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Teilweise gefördert durch das fortüne-Programm der Medizinischen Fakultät des Universitätsklinikum Tübingen (Projektnummer 1211056 und 777–0-0).

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Nohé, B., Johannes, T., Schmidt, V. et al. Einfluss verminderter Scherkräfte auf Entzündungsreaktionen in vitro. Anaesthesist 54, 773–780 (2005). https://doi.org/10.1007/s00101-005-0852-z

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