EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN IN BRONCHIAL EPITHELIUM AFTER LUNG TRANSPLANTATION IN THE RAT

Background: The normal, mature airway epithelium in experimental anima ls has a very slow cell turnover and minimal proliferation. The aim of this study was to investigate the expression of proliferating cell nu clear antigen (PCNA) as an index of bronchial cell proliferation in th e Brown Norway to Lewis rat pulmonary allograft model with or without immunosuppression. Methods: Brown Norway left lungs were transplanted into Lewis recipients. Some recipients were treated with a high dose o f cyclosporine and FK506. Lewis-to-Lewis donor-recipient combination w as performed as a control. Lungs were excised on postoperative days 3 and 5. Routinely processed, paraffin-embedded sections were prepared a nd stained by PCNA. Counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchial surface epithelium were compared wit h the histologic grade of rejection. Results: The PCNA index (percent of nuclei immunostaining for PCNA) in bronchial surface epithelium was significantly higher in allografts (21.0% +/- 3.1% at 3 days, 31.4% /- 9.8 % at 5 days, p < 0.05) than in isografts (5.4% +/- 3.0% at 3 da ys, 4.7% +/- 4.6% at 5 days). The PCNA index was also greater in the p erivascular infiltrates of rejecting lungs (23.9% +/- 3.7% at 3 days, 29.1% +/- 6.6% at 5 days). However, in the cyclosporine- and FK506-tre ated groups, the PCNA index in bronchial surface epithelium was suppre ssed to less than 5% at 3 and 5 days. Even at 50 days after transplant ation, PCNA-positive cells were rare in bronchial epithelium of FK506- treated grafts. Conclusions: Bronchial epithelium in isografts has a r elatively low rate of proliferation. In rejection, allografts have a v ery rapid cell turnover and proliferation. Proliferating epithelium ma y be a consequence of immune events or it may contribute to the pathog enesis of those events.