Compatible solutes prevent lung inflammation and loss of CFTR induced by combustion-derived nanoparticles in human and rodent experimental systems.

The compatible solute ectoine is known to attenuate inflammatory effects in the airways after exposure to combustion-derived nanoparticles. Proinflammatory 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 on airway inflammation of additional substances originating from the ectoine metabolism, NADA and 5-hydroxyectoine, in a mouse model and in human neutrophilic granulocytes. Furthermore, effects of these substances on the loss of CFTR, as an additional pathogenic endpoint of nanoparticle exposure was investigated. All three substances exhibited beneficial effects at the level of inflammatory cells in lung lavages from exposed mice. The loss of CFTR in lung tissue of exposed mice was mitigated by the substances. In primary human neutrophils and in neutrophilic differentiated HL-60 cells the reduction of apoptosis rates after particle exposure was effectively abolished. The loss of CFTR from cytoplasmic membrane in neutrophilic cells was also counteracted by the substances. The data identify both NADA and 5-hydroxyectoine as additional substances for molecular prevention of airway effects of environmental particles. Furthermore, the reduction of CFTR loss might be a relevant finding for patients suffering from impaired function of this ion channel.