RESPIRATORY VIRAL-INFECTIONS AGGRAVATE AIRWAY DAMAGE CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chro nic rejection is assumed to be the most important cause of bronchiolit is obliterans. However, viral infections might also be potential cause s of airway damage after lung transplantation. In the present study, w e investigated whether viral infections could induce airway damage in rat lung transplants in the absence or presence of chronic rejection. We compared the histopathology of the airways in 3 groups of rats: (1) nontransplanted LEW lungs, (2) LEW-to-LEW syngeneic lung transplants, and (3) BN-to-LEW allogeneic lung transplants. Nontransplanted and tr ansplanted rats were treated with CsA to induce permanent graft accept ance of the allografts. Six months after transplantation, 4 noninfecte d rats of each group were killed for histological investigation (anoth er 4 noninfected allografted rats were killed 56 days later). The rema ining 16 rats in each group were infected with Sendai virus (parainflu enza type 1) intratracheally. These rats were killed for histological investigation 4, 7, 21, and 56 days after infection. In the lungs of t he noninfected rats of the nontransplanted and syngeneically transplan ted groups, airway changes were absent. After viral infection in these lungs, mild inflammation developed in the airways that was transient and completely resolved by day 56 after infection. In contrast, in the allogeneically transplanted lungs the viral infection caused severe a nd permanent damage of the airways. In the bronchioles and the large a irways throughout the allogeneic lung transplants, inflammation with e pithelial necrosis and formation of granulation tissue was present. On day 56 after infection, the bronchioles showed scarring in the submuc osa and obliteration of the lumen, typical features of bronchiolitis o bliterans. This study shows that a respiratory viral infection aggrava tes the airway damage in rat lung allografts with chronic rejection. T he findings suggest that viral infections and chronic rejection play a synergistic role in the development of bronchiolitis obliterans after human heart-lung and lung transplantation: the virus infection may st imulate chronic rejection and rejection may hamper the local defense a gainst the virus.