Diverging Proliferative Behavior of Alveolar Epithelial Cells in Progressive Elastase-Induced Emphysema

• Published in: Pneumologie
• Main Authors: Bohla, A, Kohse, K, Schwarz, J, John, G, Amarie, OV, Eickelberg, O, Yildirim, AÖ
• Format: Conference Proceeding
• Language: English
• Published: 31.05.2012
• ISSN: 0934-8387; 1438-8790
• DOI: 10.1055/s-0032-1315495

Rationale: Development of emphysema is typical for chronic obstructive pulmonary disease (COPD). We already showed that a single application of porcine pancreatic elastase (PPE) causes a severe progressing emphysema-like phenotype in C57BL/6 mice. Emphysema formation is apparently not completed after PPE application, so we aimed to identify possible key mechanisms that drive this process even at late time points. Methods: Female C57BL/6 mice received a single oropharyngeal application of PPE or PBS, and lung function, histology and gene expression was analyzed on day 2, 28, 56, and 162. Fibroblasts of PPE treated mice were characterized analyzing mitochondrial membrane potential. Furthermore, LA-4 lung epithelial type 2 cells were treated with PPE and proliferative and apoptotic characteristics were measured using gene expression or functional wound healing assays. Results: Correlation of progressive airway enlargement and impairment of pulmonary function could be observed during 23 weeks of analysis of PPE treated C57BL/6 mice. QRT-PCR revealed elevated expression of apoptotic markers, reduced proliferation and increased expression of extracellular matrix components. Interestingly, isolated lung fibroblasts of PPE treated mice demonstrate reduced proliferation and an altered mitochondrial membrane potential as a marker for impaired regeneration. Furthermore, decreased proliferation and impaired wound healing was also found in PPE treated LA-4 cells. Conclusion: We found diminished proliferation in PPE treated lung epithelial cell lines as well as in lungs and primary lung fibroblasts of PPE treated mice, which could explain the persistent progression of PPE induced emphysema in mice.