A novel mouse model reproducing pathomorphological and inflammatory hallmarks of COPD

Chronic Obstructive Pulmonary Disease (COPD) is a severe progressive disease without effective curative therapy options. Current research strongly relies on pre-clinical models to gain mechanistic insights, identify new therapeutic targets and to test new curative interventions. Despite recapitulating several aspects of human disease, frequently used COPD models, such as elastase or cigarette smoke (CS) exposure, are limited by either only reproducing pathomorphological changes (elastase) or are excessively time consuming (chronic smoking, 3-6 months). Here we have characterized a novel COPD mouse model presenting with a moderate emphysema and pulmonary inflammation, based on the main smoke toxin Acrolein combined with lipopolysaccharide (LPS) exposure. Functional and pathological changes were characterized by lung function measurements, histology and inflammatory profiling. Acrolein/LPS mice possessed mild to moderate emphysema and bronchial remodeling characterized by increased airway epithelial thickness and goblet cells. Flow cytometry revealed significant increases in several immune cells, such as CD4, CD8 T-cells, macrophages and dendritic cells. In summary, the LPS/Acrolein mouse model reproduces several hallmarks of human COPD; is simple to handle and reproducible. This model may provide new mechanistic insights, aid target identification, and test new curative interventions.