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Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation

Sydlik, Ulrich, Peuschel, Henrike, Paunel-Görgülü, Adnana, Keymel, Stefanie, Krämer, Ursula, Weissenberg, Alexander, Kroker, Matthias, Seghrouchni, Samira, Heiss, Christian, Windolf, Joachim , Bilstein, Andreas, Kelm, Malte, Krutmann, Jean and Unfried, Klaus (2012) Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation European Respiratory Journal, 41 (2). pp. 433-442.

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Abstract

The life span of neutrophilic granulocytes has determining impact on the intensity and duration of neutrophil driven lung inflammation. Based on the compatible solute ectoine, we aimed to prevent anti-apoptotic reactions in neutrophils triggered by the inflammatory microenvironment in the lung.

Neutrophils from COPD patients and control individuals were exposed to inflammatory mediators and xenobiotics in the presence or absence of ectoine. The in vivo relevance of this approach was tested in xenobiotic-induced lung inflammation in rats.

The reduction of apoptosis rates of ex vivo exposed neutrophils from persons of all study groups was significantly restored in the presence of ectoine. However, natural apoptosis rates not altered by inflammatory stimuli were not changed by ectoine. Mechanistic analyses demonstrated the preventive effect of ectoine on the induction of anti-apoptotic signalling. Neutrophilic lung inflammation induced by single or multiple exposition of animals to environmental particles was reduced after the therapeutic intervention with ectoine. Analyses of neutrophils from bronchoalveolar lavage indicate that the in vivo effect is due to the restoration of neutrophil apoptosis.

Ectoine, a compound of the highly compliant group of compatible solutes, demonstrates a reproducible and robust effect on the resolution of lung inflammation.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Clinical and Experimental Medicine
Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
Sydlik, Ulrich
Peuschel, Henrike
Paunel-Görgülü, Adnana
Keymel, Stefanie
Krämer, Ursula
Weissenberg, Alexander
Kroker, Matthias
Seghrouchni, Samira
Heiss, Christianc.heiss@surrey.ac.uk
Windolf, Joachim
Bilstein, Andreas
Kelm, Malte
Krutmann, Jean
Unfried, Klaus
Date : 25 October 2012
Identification Number : 10.1183/09031936.00132211
Copyright Disclaimer : Copyright 2012 by the European Respiratory Society
Uncontrolled Keywords : Carbon black; Chronic obstructive pulmonary disease; Emphysema; Granulocyte-macrophage colony-stimulating factor; Leukotriene B4; Phosphatidylinositol 3-kinase;
Depositing User : Diane Maxfield
Date Deposited : 16 Aug 2018 15:11
Last Modified : 16 Aug 2018 15:11
URI: http://epubs.surrey.ac.uk/id/eprint/848994

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