Increased endothelin-1 associated with bacterial infection in lung transplant recipients

Background. Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infect ious processes. Episodes of infection are suspected to be involved in the d evelopment of bronchiolitis obliterans syndrome (BOS), which is the main fe ature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS, We, the refore, set up this study to assess ET-1 expression in relation to complica tions of the graft in human lung transplant recipients. Methods. ET-1 mRNA was quantified by reverse transcription-competitive poly merase chain reaction in cells from 119 samples of bronchoalveolar lavage ( BAL) fluid from 17 lung transplant recipients. ET-1 and big ET-1 proteins w ere assessed in BAL cell culture supernatants by enzyme immunoassay. Transb ronchial biopsies (n=21) were stained immunohistochemically for ET-1 recept ors. Results. Episodes of bacterial infection strongly correlated with increased ET-1 mRNA and protein expression. ET-1 receptors were also upregulated dur ing these episodes, especially on endothelial and smooth muscle cells. Five of the seven patients with the highest ET-1 levels subsequently developed BOS. Conclusions. These results raise the possibility that ET-1, part of whose p roduction is triggered by infectious postgraft complications, might play a role in the development of BOS through its potential effects on airway remo deling.