PURPOSE: Obliterative bronchiolitis (OB) remains the main limitation on long-term survival of lung transplantation. OB is a manifestation of chronic allograft rejection with histological features of epithelial cell injury, inflammation, fibrosis, and obliteration of small airways. An intact respiratory epithelium prevents OB development. This study focused on influence of epithelial chimerism on chronic allograft rejection in a pig model of OB.
METHODS: Random-bred pigs with adequate, inadequate or no immunosuppression received a series of bronchial implants, 1.5 cm in length, subcutaneously on the ventral side. In 9 male recipients with allografts from female donors and in 2 males with control autografts, grafts were serially obtained. Histology (H&E) and fluorescence in situ hybridization (FISH) method for Y chromosome using pig-spesific DNA-label were assessed. Additional 5 female recipients received bronchial allografts from male donors. Samples of lung, liver, kidney and spleen were ob-tained after 3 months to study Y chromosomes (FISH) in female recipient organs.
RESULTS: In study animals, no adverse effects were observed. In bronchial allografts with none or inadequate im-munosuppression, rapid epithelial destruction occurred preceding obliteration. Adequate immunosuppression resulted in permanent graft patency (p < 0.001) and in delay of Y chromosome positivity. However, after appear-ance, Y chromosomes stained intense throughout 3 months. Early appearance of recipient-derived cells into the airway epithelium appeared predictive of epithelial destruction (R = 0.610 - 0.671 and p < 0.05) and of oblitera-tion of the bronchial lumen (R = 0.698 and p < 0.01). Chimeric cells in lung, liver, kidney or spleen were not observed.
CONCLUSION: Ingraft chimerism may be a mechanism to repair alloimmune-mediated tissue injury after transplantation.
CLINICAL IMPLICATIONS: High number of chimeric cells in transplanted lungs may allow reduction of the immunosuppressive regimen.
DISCLOSURE: Paula Maasilta, No Financial Disclosure Information; No Product/Research Disclosure Information