Lung Xenotransplantation in the Rat Lung Xenotransplantation in the Rat

The aim of this study was to investigate the functional and morphological aspects of orthotopic lung xenograft rejection in a concordant hamster-to-rat donor-recipient species combination. All transplanted lungs had infiltrates during the 3 postoperative days. Complement-dependent cytotoxicity assays revealed that anti-hamster lymphocytotoxic antibody titer increased to 5.2±1.1 (p < 0.05 vs. 1 day) 3 days after transplantation and reached 9.8±0.5 (p < 0.05 vs. 1, 3 and 5 days) 7 days after transplantation. Titers were not elevated 1 day after transplantation. The CD4+/CD8+ ratio in peripheral blood lymphocytes increased significantly at 3 days (p < 0.05, versus untransplanted) . At 5 th day, the ratio was lower than at 3 rd day (p < 0.05). There was no significant difference in B-cell population between rats before grafting and each group. Histologically, xenotrasplanted grafts were characterized by perivascular cellular infiltrates and edema 3 days after transplantation. The inflammatory infiltrate formed a dense cuff around the venules and arterioles. At 5 th day, arteriolar lumenal narrowing was observed, and air-space containing many alveolar macrophages and lymphocytes. Immunohistochemical analysis of these grafts showed strong IgM and C3 deposits in the vascular endothelium, without any igG deposits. No IgM, C3 or IgG deposits were observed in normal hamster lung. This study indicates that both the cellular and humoral immune system mediate primary acute rejection in the hamster-to-rat orthotopic lung xenograft model.