Chronic lung allograft pathology lesions in two rat strain combinations

BACKGROUND: Chronic lung allograft dysfunction remains an obstacle to long-term survival after lung transplantation. Two phenotypes have been described: obliterative bronchiolitis and restrictive allograft syndrome. Preclinical models are essential to analyze chronic lung allograft dysfunction pathophysiology. METHODS: Orthotopic lung transplants from 38 Lewis into Fischer 344 (Lew→F344) and 67 Brown-Norway into Lewis (BN→Lew) rats were performed in our center in the last decade. We carefully reviewed and quantified all grafts with chronic rejection (40 cases) (18 Lew→F344, 22 BN→Lew) with the aim to investigate if histological changes of chronic lung allograft dysfunction could be also detected in rat grafts. RESULTS: All animals showed human reminiscent histological lesions. Early chronic rejection lesions were detected in BN→Lew. End-stage chronic rejection with features of obliterative bronchiolitis was observed in 33% of Lew→F344; end-stage with restrictive allograft syndrome chronic rejection in 67% and 80% of Lew→F344 and BN→Lew, respectively. BN→Lew showed higher grades of endotheliitis, vascular fibrosis, and lower grades of lymphoid aggregates than Lew→F344 (P=0.007, P=0.043, P=0.004, respectively). CONCLUSIONS: Chronic rejection lesions in rat lung allografts mimic those in humans. The frequent occurrence of restrictive allograft syndrome-like lesions in BN→Lew may be related to a higher degree of mismatch in this strain combination. These animal models could allow future mechanistic studies to better understand chronic lung allograft dysfunction pathogenesis.