Expression of proliferating cell nuclear antigen in bronchial epithelium after lung transplantation in the rat.
BACKGROUND
The normal, mature airway epithelium in experimental animals has a very slow cell turnover and minimal proliferation. The aim of this study was to investigate the expression of proliferating cell nuclear antigen (PCNA) as an index of bronchial cell proliferation in the 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 of cyclosporine and FK506. Lewis-to-Lewis donor-recipient combination was performed as a control. Lungs were excised on postoperative days 3 and 5. Routinely processed, paraffin-embedded sections were prepared and stained by PCNA. Counts of PCNA-positive cells in the perivascular cellular infiltrate and bronchial surface epithelium were compared with 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 days, 4.7% +/- 4.6% at 5 days). The PCNA index was also greater in the perivascular infiltrates of rejecting lungs (23.9% +/- 3.7% at 3 days, 29.1% +/- 6.6% at 5 days). However, in the cyclosporine- and FK506-treated groups, the PCNA index in bronchial surface epithelium was suppressed to less than 5% at 3 and 5 days. Even at 50 days after transplantation, PCNA-positive cells were rare in bronchial epithelium of FK506-treated grafts.


CONCLUSIONS
Bronchial epithelium in isografts has a relatively low rate of proliferation. In rejection, allografts have a very rapid cell turnover and proliferation. Proliferating epithelium may be a consequence of immune events or it may contribute to the pathogenesis of those events.
Nagayasu
T
T
First Department of Surgery, Nagasaki University School of Medicine, Japan.
Oka
T
T
Sawada
T
T
Tamura
K
K
Shirafuji
T
T
Ryu
C
C
Ayabe
H
H
D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D016572:Cyclosporine / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016040:Lung Transplantation; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis* / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D018809:Proliferating Cell Nuclear Antigen; D016572:Cyclosporine; D016559:Tacrolimus