Project Details
Projekt
mechanisms of airflow-induced mechanoreception/-transduction and their impacts on ventilation associated lung injury
Subject Area
Anaesthesiology
Term
from 2014 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 259162749
Ventilator associated lung injury is a serious complication in critical ill patients and is characterized by a disturbed alveolo-epithelial barrier function as well as a compromised alveolar fluid reabsorption. Ventilator associated lung injury is typically described as an inflammatory response based on cell stretch induced mechanoreception and mechanotransduction in the alveolar epithelium. However, little is known about the airflow- induced shear stress at the bronchial and alveolar level. This study proposal aims to describe the existence of the epithelial mechanoreception and subsequent signal transduction in distal airway epithelial cells as a consequence of airflow induced shear stress. For this purpose we developed a chamber to apply airflow induced shear stress on distal airway epithelial cells. To translate these findings it is planned to confirm the results in animal experiments. Preliminary results in cultured alveolar epithelial cells suggest that airflow induced shear stress leads to a reactive oxygen species mediated Ca2+ influx and increased liberation of mitochondrial reactive oxygen species. We could demonstrate that the degradation of the epithelial glycocalix, which plays a major role in the mechanoreception of blood flow induced endothelial shear stress, increased the airflow induced Ca2+ signal. A degradation of the glycocalix has been shown to be a consequence of bacterial induced inflammation. Therefore we would like to investigate as well how the increased Ca2+ signal after glycocalix degradation is generated and if this mechanism can explain the observation that the lungs are more susceptible to ventilator associated lung injury after an initial inflammatory stimulus.
DFG Programme
Research Grants
