Lung inflammation is significantly reduced by recovery of neutrophil apoptosis in vivo

Abstract

INTRODUCTION: Neutrophil apoptosis is considered to be a major regulator of neutrophil driven lung inflammation. The compatible solute ectoine has been described to act preventive against lung inflammation induced by environmental particles (Sydlik et al., Am J Respir Crit Care Med 2009). As a therapeutic approach, here, we investigated the influence of this compound on neutrophil apoptosis in the inflammatory microenvironment.

METHODS: Human neutrophils were treated ex vivo with particles or inflammatory mediators in the presence or absence of ectoine in order to study apoptosis rates and pro-apoptotic signalling. Lung inflammation was induced in rats by intra-tracheal application of 2.5 mg/kg environmental particles and studied in lung lavages after control or ectoine intervention.

RESULTS: Apoptosis rates of human neutrophils from COPD patients and volunteers, which were significantly reduced by the inflammatory stimuli, recovered significantly in the presence of ectoine. Mechanistic analyses demonstrated the preventive effect of ectoine of pro-apoptotic signalling events via Akt and Mcl-1. The in vivo relevance of the data was shown by significantly reduced neutrophil inflammation after ectoine intervention which correlated with restored neutrophil apoptosis rates in the lung.

CONCLUSIONS: The current studies demonstrate the effectivity to prevent anti-apoptotic signalling in neutrophils by the compatible solute ectoine. This effect led to recovered apoptosis rates and a reduction of environmentally induced lung inflammation. The relevance of ectoine treatment for humans is demonstrated by the EFECT study which will be presented on the same meeting.