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.

Ectoine-Containing Cream in the Treatment of Mild to Moderate Atopic Dermatitis: A Randomised, Comparator-Controlled, Intra-Individual Double-Blind, Multi-Center Trial

“…This adhesion molecule is a hallmark of inflammatory skin diseases such as psoriasis and AD [28]. In animal experiments, ectoine has also been found to protect against nanoparticle-induced neutrophilic lung inflammation, regardless of whether it is given with or before the nanoparticle [29,30]. Taken together, these studies strongly indicate that ectoine has anti-inflammatory properties.…”

Signalling-Dependent Adverse Health Effects of Carbon Nanoparticles Are Prevented by the Compatible Solute Mannosylglycerate (Firoin) In Vitro and In Vivo

“…Protein isolation and Western blotting were performed as described earlier [5],[9],[23] using antibodies specific for phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204), and phospho-SAPK/JNK (Thr183/Tyr185). Total ERK1/2, JNK1/2, and GAPDH (Imgenex, San Diego, CA) proteins were monitored with p44/42 MAPK and SAPK/JNK antibodies, respectively.…”

“…CNP-specific activation of the MAPK p38 leads to an up-regulation and increased release of the pro-inflammatory chemokine IL-8 [8]. In neutrophilic granulocytes, CNP trigger specific membrane-dependent signalling pathways which reduce the natural apoptosis rates of these immune cells and therefore contribute to the aggravation of the inflammation [9].…”

“…More recently, we were able to show that CNP in an ongoing inflammation reduce the natural apoptosis of neutrophils and therefore contribute to the aggravation of the inflammation. In this scenario, the application of ectoine restored natural apoptosis rates by preventing adverse membrane-coupled signalling in neutrophils and thereby led to a reduction of neutrophilic lung inflammation [9].…”

Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

“…Currently, studies are performed to investigate if some of these drugs, such as p38 inhibitors, can be used for COPD, where they can be administered locally via inhalation [129]. A very promising new drug, ectoine is able to restore normal apoptosis of neutrophils, which would lead to both lower levels of neutrophils in the lung and to less instances of neutrophil necrosis, thus also decreasing the protease/antiprotease imbalance [130]. Because this drug only restores the normal lifespan of neutrophils, it does not affect the normal functioning of this cell type, which has been the main drawback of many other drugs.…”