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

Abstract

The life span of neutrophilic granulocytes has a 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 chronic obstructive pulmonary disease 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 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 expositions 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.

• Authors: Ulrich Sydlik, Henrike Peuschel, Adnana Paunel-Görgülü, Stefanie Keymel, Ursula Krämer, Alexander Weissenberg, Matthias Kroker, Samira Seghrouchni, Christian Heiss, Joachim Windolf, Andreas Bilstein, Malte Kelm, Jean Krutmann, Klaus Unfried
• Journal: The European respiratory journal (Eur Respir J) Vol. 41 Issue 2 Pg. 433-42 (Feb 2013) ISSN: 1399-3003 [Electronic] England
• PMID: 23100492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids, Diamino
• Soot
• Xenobiotics
• Leukotriene B4
• ectoine
• Granulocyte-Macrophage Colony-Stimulating Factor
• Phosphatidylinositol 3-Kinases

Topics

• Adult
• Aged
• Amino Acids, Diamino (pharmacology)
• Animals
• Apoptosis
• Case-Control Studies
• Cells, Cultured
• Emphysema (metabolism)
• Female
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Inflammation (drug therapy, pathology)
• Leukotriene B4 (metabolism)
• Lung (pathology)
• Male
• Middle Aged
• Neutrophils (drug effects, pathology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Pulmonary Disease, Chronic Obstructive (metabolism)
• Rats
• Rats, Inbred F344
• Soot (pharmacology)
• Xenobiotics (pharmacology)