Stimulation beta-adrenerger Rezeptoren auf neutrophilen Granulozyten - Effekte auf Adhäsionsmoleküle, Zytokine und intrazelluläre Botenstoffe

In der vorliegenden Arbeit wurden unstimulierte und vorstimulierte neutrophile Granulozyten aus dem Blut gesunder Spender mit Adrenalin und Noradrenalin inkubiert. Auf der Ebene der Signaltransduktion adrenerger Rezeptoren wurden die intrazelluläre cAMP-Konzentration und der Kalzium-Influx nach Inku...

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Bibliographic Details
Main Author: Greulich, Timm
Contributors: von Wichert, Peter (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2005
Innere Medizin
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Table of Contents: Aims: To evaluate the impact of catecholamines on cytokine production and expression of adhesion molecules by human neutrophils in vitro. Methods: Neutrophils were separated from venous blood of healthy subjects. The generation of intracellular cAMP and Ca++ was determined after incubation with catecholamines. Resting and lipopolysaccharide (LPS)-activated neutrophils were tested für synthesis of IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha). In addition, the expression of the adhesion molecules CD15, CD44, and CD54 was evaluated in resting and activated neutrophils. Increasing concentrations (1 nM - 1 µM) of epinephrine (EPI) were used to study the influence of activation of beta2-adrenergic receptors (beta2R) on cytokine production and adhesion molecule expression. Results: Icubation with catecholamines induced an increase in cAMP but not Ca++ in neutrophils. Only IL-8 was detected followin stimulation with LPS and was unchanged upon co-incubation with EPI. The expression of CD15 and CD44 decreased spontaneously in vitro. The density of CD44 increased in the presence of very high doses of EPI (1 µM). CD54 was expressed on activated neutrophils only. The density of CD54 on neutrophils was lower upon co-incubation with 1 µM EPI for 6 h. However, the expression of CD54 on neutrophils increased upon incubation with 1 µM EPI for 18 h. Conclusions: beta2R are functionally coupled to signalling cascades in human neutrophils. Nevertheless, the impact of catecholamines in IL-8 synthesis and expression of CD15, CD44, and CD54 is limited.