Integrity of airway epithelium is essential against obliterative airway disease in transplanted rat tracheas

Background: The pathogenesis of obliterative bronchiolitis after lung transplantation requires further elucidation. In this study we used rat trachea transplantation to examine the role of epithelium in the progression of obliterative airway disease.Methods: Normal and denuded (i.e., epithelium removed) trachea grafts from Lewis (LEW) and Brown Norway (BN) rats were transplanted sub-cutaneously into LEW rats. Viable trachea epithelial cells (to recover epithelium) were seeded into the lumen of some of the denuded tracheas. Grafts were removed at different time-points between 2 days and 8 weeks after transplantation. Histologic analysis was performed to evaluate cellular infiltration of inflammatory cells, loss of epithelium, and obliteration of trachea lumen.Results: Obliteration was found to occur in trachea transplants after loss of epithelium, caused by rejection in allografts or by enzymatic denudation in isografts. In these situations, fibroblasts started to proliferate and migrate into the lumen in the second week after transplantation. Obliteration could be prevented when epithelial integrity was restored by seeding epithelial cells; no obliteration occurred when denuded trachea isografts were seeded with epithelial cells, whereas non-seeded denuded tracheas were obliterated at Day 6 after transplantation.Conclusions: We conclude that integrity of air-way epithelium is essential for rat trachea transplants to be safeguarded from obliterative airway disease. For clinical lung transplantation the results of our study suggest that protection of the integrity of airway epithelium may be important in preventing the development of obliterative bronchiolitis.