Early and long-term graft and patient survival after lung transplantation are challenged by chronic lung allograft dysfunction (CLAD), whose main phenotype is represented by bronchiolitis obliterans syndrome (BOS), a condition characterized by an irreversible obstructive graft dysfunction due to fibro-obliterative lesion of small airways. Based on the anti-inflammatory and anti-protease properties of Alpha-1 antitrypsin (AAT), specifically versus neutrophil elastase (HNE), a possible role of this protease inhibitor in short and long term outcome after lung transplantation has been recently underlined by an increasing number of studies. In the present research a multidisciplinary procedure, which included electrophoresis/western blotting coupled to mass spectrometric analysis and combined with the functional evaluation of the residual antiprotease activity was applied to investigate the relationship between HNE and AAT in BALf from stable lung transplant recipients and BOS patients. While demonstrating by MS, for the first time, the formation in real samples of the complex between HNE and AAT, our findings also show that this complex is not present in all BALf specimens analyzed. The neutrophil count and the determination of HNE and AAT activities suggested that the lack of the complex in some subjects could be correlated with their low level of lung inflammation. If these findings prove true on a larger number of BALfs, they may point to the formation of HNE-AAT complex as a possible biomarker of pulmonary inflammation level in this disorder.
Maddalena Cagnone is a PhD student in Biomedical Science (curriculum Biochemistry) at the Department of Molecular Medicine of the University of Pavia (Italy). She graduated in “Experimental and Applied Biology” at the University of Pavia. After graduation, she obtained a scholarship to study the expression of CD44 on mesenchymal cells from patients with different degree of chronic lung rejection. In the course of this first PhD year, she has been studying the role of AAT in BALf of transplant patients.