OP 16. The Role of Adrenomedullin in Bronchiolitis Obliterans Syndrome


B. Gieszer, M. Gyugos, J. Tóvári, J. Fillinger, K. Török, A Farkas, G. Lang, B. Döme, F. Rényi-Vámos

Chair(s): László Kóbori, Thomas van Gulik & Dávid Ágoston Kovács

12:30 - 12:40h
Categories: Organ and Cell Transplantation, Oral Session

Session: Oral Sesion II - Organ and Cell Transplantation


Background:
The long-term success of lung transplantation (LTx) is mainly limited by bronchiolitis obliterans syndrome (BOS), the manifestation of chronic rejection. Injury of allograft epithelium is the main complication of chronic rejection. Release of cytokines from the injured epithelial cells and chemokines makes T-cells, neutrophil granulocytes and macrophages infiltrate the graft tissue. Human adrenomedullin (AM) peptide (consisting of 52 amino acids) has an important role in (lymph)angiogenesis, tumor progression, immune- and endocrine processes and, moreover, via the protection of epithelium and endothelium, in the alveolar development of lung as well as. Our aim is to study the effect of AM in the development of BOS and to investigate the epithel- protecting role of AM in vivo.

Material and Methods:
The efficacy of AM and AM inhibitors were studied in a BOS-mouse model. Heterotopic tracheal transplantation was performed between MHC-fully allogeneic mismatched mice and treated with AM and AM inhibitors.

Result:
We expect that AM will exert protective effects on the epithelium and endothelium, due to its potential to decrease endothelial permeability. AM might also reduce the extravasation of immune cells. These effects may decrease the number of inflammatory cells migrating to the tissue graft and AM might reduce the fibrosis and obliteration of the graft. This study might serve as valuable tool for therapeutic approaches in patients after LTx.

Conclusion:
Acknowledgement: This study was supported by the OTKA K108465 grant. Further support: TÁMOP424A/1-11-1- 2012-0001 (B Dome); KTIAAIK12-1-2013-0041 (B Dome, J Tovari J, F Renyi-Vamos)