Role of Alpha 1-antitrypsin and Human Neutrophil Elastase in BALf of lung transplant recipients: preliminary data

Long-term survival after lung transplantations is still poor, mainly due to chronic lung allograft dysfunction, with its most frequent phenotype being bronchiolitis obliterans syndrome (BOS), characterized by a high neutrophil recruitment. Given the multiple therapeutic benefits of alpha1-antitrypsin (AAT) -including inhibition of neutrophil elastase activity- in the past years few studies were published, suggesting that the interaction between AAT and the human neutrophil elastase (HNE) may play a role in the graft acceptance after lung transplantation. Our aim is to study the concentration of AAT and HNE in Bronchoalveolar Lavage fluid (BALf) from lung recipients, and their effects in long-term graft acceptance. We tested BALf of a limited number of selected stable lung transplant recipients (27) and patient affected by BOS at different grade (BOS0p n=10, BOS1-3 n=17). This preliminary results showed a clear but non significant trend of AAT levels which were higher in BALf from stable patients (1,53 mg/dL) compared to BOS 0p (0,82 mg/dL) and BOS1-3 patients (0,35 mg/dL). The measurement of free HNE activity were significantly lower (p=0,02) in stable patients (0,085 mU/mg) with respect to BOS (0,760 mU/mg). Electrophoresis, combined with Western blotting analysis, allowed to observe different forms of AAT (AAT-HNE complex; free form of AAT; degraded forms) in different samples. These data suggested that, while being present, AAT is not always able to react effectively to all proteases, produced by biochemical inflammation/immune-related processes. The role of AAT in the development of major complications in lung transplant recipients deserves further investigation.