Chronic rejection of experimental lung allografts

• Applicant: Professorin Dr. Veronika Grau
• Subject Area: General and Visceral Surgery
• Term: from 2009 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 162638346

Survival of lung transplant recipients is limited by the development of bronchiolitis obliterans syndrome (BOS). Risk factors and experimental evidence suggest that BOS is a chronic allograft rejection enhanced by infections. The pathogenesis of BOS is poorly understood, currently immedicable, and existing experimental models are disputable. We have developed a rat model resulting in a histopathology similar to human BOS, which involves lung transplantation, suboptimal immunosuppression and intratracheal application of the irritant lipopolysaccharide. Functional and histopathological aspects of this model will be compared to human BOS. Graft infiltrating leukocytes and cells accumulating in graft blood vessels will be investigated. To identify new molecular pathways, systematic transcriptome analyses of isolated graft compartments will be performed. Differential expression of selected genes and their therapeutical potential will be scrutinized. In addition, we will evaluate endothelin receptor antagonists, a therapy for pulmonary hypertension, for the treatment of BOS in rats, which may result in rapid clinical application. In summary, this project systematically elucidates critical steps in the pathogenesis of BOS and develops novel specific therapeutic strategies.

• DFG Programme: Research Grants