Effect of AAT augmentation therapy on bronchiolitis obliterans development in mice model

Obliterative bronchiolitis (BO) is one of the major limitations to long-term survival after lung transplantation (LuTx), which is recognized as a major factor of chronic lung allograft dysfunction (CLAD). Acute rejection is a significant risk factor that leads to BO development. Therefore, therapeutic strategies limiting the severity of acute inflammation can be of critical importance in preventing acute rejection episodes and BO.  Both preclinical and clinical experiences show that the therapy with plasma-purified alpha1-antitrypsin (AAT) is beneficial for a broad spectrum of inflammatory conditions. We previously demonstrated that therapy with AAT suppresses the acute rejection after LuTx in a mouse model. Herein, we aimed to investigate if prophylactic therapy with AAT prevents BO development in an orthotopic single LuTx model (C57BL/10 as donors and C57BL/6 as recipients) mice model. Transplanted mice were treated with cyclosporine (15 mg/kg) alone in the first week every day or with cyclosporine administration combined with AAT therapy (5 mg/kg) twice a week until the sacrifice 8 weeks after the LuTx. As illustrated in figure 1, mice not receiving AAT therapy (controls, n=5) develop BO and lung rejection whereas those receiving AAT therapy (n=3) did not develop BO and show only mild acute rejection. The beneficial effects of AAT seem to involve the anti-protease and immunomodulatory activities of AAT. AAT therapy may lower inflammatory responses due to ischemic inju...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of lung injury and repair Source Type: research