# Compatible Solutes Prevent Lung Inflammation and Reduction in CFTR Induced by Combustion-Derived Nanoparticles in Human and Rodent Experimental Systems

## TL;DR

This study shows that compatible solutes like ectoine, NADA, and 5-hydroxyectoine can prevent lung inflammation and CFTR reduction caused by nanoparticle exposure in both mice and human cells.

## Contribution

The study identifies NADA and 5-hydroxyectoine as new preventive agents against nanoparticle-induced lung effects.

## Key findings

- All three solutes reduced inflammation in lung lavages from nanoparticle-exposed mice.
- The solutes counteracted the nanoparticle-induced decline in CFTR in lung tissue and neutrophilic cells.
- Apoptosis delay in human neutrophils after particle exposure was effectively reversed by the solutes.

## Abstract

The compatible solute ectoine is known to attenuate inflammatory effects in the airways after exposure to combustion-derived nanoparticles. Pro-inflammatory signaling in epithelial cells, as well as antiapoptotic mechanisms in neutrophilic granulocytes, both triggered by particles, are reduced by this substance. Here we investigated the preventive potential in airway inflammation of additional compounds originating from the ectoine metabolism, Nγ-acetyl-L-2,4-diaminobutyric acid (NADA), and 5-hydroxyectoine in a mouse model and in human neutrophilic granulocytes. Furthermore, effects of these molecules on the reduction in cystic fibrosis transmembrane conductance regulator (CFTR), as an additional pathogenic endpoint of nanoparticle exposure, were investigated. All three solutes exhibited beneficial effects at the level of inflammatory cells in lung lavages from exposed mice. The decrease in CFTR in lung tissue of exposed mice was mitigated by the substances. In primary human neutrophils and in neutrophilic differentiated HL-60 cells, the delay of apoptosis rates after particle exposure was effectively abolished. The decline in CFTR from the cytoplasmic membrane in neutrophilic cells was also counteracted by the compatible solutes. The data identify both NADA and 5-hydroxyectoine as additional substances for molecular prevention of airway effects of environmental particles. Furthermore, the reduction in CFTR might be a relevant finding for patients suffering from impaired function of this ion channel.