(L-467) Dose Dependent Response to Extracellular Matrix Nanoparticles in Lipopolysaccharide-Induced Lung Injury

Acute respiratory distress syndrome (ARDS) is a severe form of lung injury with a high mortality rate and no cure. ARDS is characterized by edema in the lung, gap formation in endothelial tissue, a decrease in lung compliance, and, ultimately, hypoxemia and fibrosis. ARDS also induces an exaggerated immune response and an acute inflammatory response. There is no distinctive cure for ARDS. Current inhaled treatments merely attempt to subdue symptoms or prevent further injury. However, because the particle size of current inhaled treatments is on the microscale, the treatment particles are not able to enter and remain in the distal alveolar regions of the lung, preventing any form of treatment at the injury site. This study utilizes a novel, electrically charged nanoparticle fabricated from xenographic, organ-specific extracellular matrix (ECM), which has been shown in vitro to be pro-regenerative and anti-inflammatory. The aim of this study is to optimize the dose of the ECM nanoparticle treatment to decrease the severity of the immune response that induces inflammation and injury. We hypothesize that a higher dose will have a more positive effect on LPS-induced lung injury.

LPS injury increases immune cell infiltration in the airspace, as shown by cell count analysis of BAL fluid. There is a sex difference in the most effective dose of nanoparticles. In female mice, the most significant decrease in cell infiltration occurs with 0.125 mg/mL (1x) of ECM nanoparticles administered. In male mice, however, a lower dose (0.0625 mg/mL, 0.5x) of ECM nanoparticles trends toward a greater decrease in cell infiltration.

While we hypothesized that higher doses of ECM nanoparticles would have a more positive effect on lung injury, our recent in vivo data has shown increased cell infiltration with the highest dose of nanoparticles. Moreover, we discovered a sex difference in the most effective dose, with male mice responding better to lower doses than female mice. To further explore these findings, our future studies will include detailed protein and cytology analysis in BAL fluid, as well as analyzing lung histology, gene expression, and plasma proteins.