REPRODUCTION OF THE OBLITERATIVE BRONCHIOLITIS LESION AFTER HETEROTOPIC TRANSPLANTATION OF MOUSE AIRWAYS

Obliterative bronchiolitis, characterized histopathologically by airwa y inflammation and occlusion of small airways by vascularized fibrous tissue, constitutes an important threat to the long-term survival of l ung and heart-lung transplant recipients. The pathogenesis of oblitera tive bronchiolitis is poorly understood, and successful preventative o r treatment strategies are not available. We sought to develop a precl inical model system of obliterative bronchiolitis by transplanting mur ine airways grafts, consisting of tracheas and main bronchi, into the subcutaneous tissue of allogeneically mismatched recipient animals. By 10 days after transplantation, allografts demonstrated subepithelial and/or peritracheal inflammation, epithelial necrosis, and early fibro proliferation. Grafts harvested 21 days after transplantation demonstr ated fibroproliferation in the airway wall or lumen in nine of 10 allo grafts versus 0 of 10 isografts (P = 0.0001). In addition, abnormal ep ithelium (ie, nonciliated cuboidal, squamous, or absent) was seen in a ll allografts, while nine of nine isografts demonstrated normal respir atory epithelium (P = 0.0003). Although differences exist between this model and the chronic rejection process in human lung transplant reci pients, these findings reproduce the characteristic features of oblite rative bronchiolitis and demonstrate that this lesion can result from allograft rejection. This model will be useful for studying the pathog enesis, prevention, and treatment of obliterative bronchiolitis after lung transplantation.