AIRWAY EPITHELIUM IS THE PRIMARY TARGET OF TRACHEAL ALLOGRAFT REJECTION IN OBLITERATIVE AIRWAY DISEASE.

1.1
#4
AIRWAY EPITHELIUM IS THE PRIMARY TARGET OF TRACHEAL ALLOGRAFT REJECTION IN OBLITERATIVE AIRWAY DISEASE.
F. Fernandez MD , A. Jaramillo PhD , C. Chen MD , T. Tung MD , G. A. Patterson, MD and T. Mohanakumar PhD . St. Louis MO, Washington University, 63110, Surgery .

Introduction: Murine heterotopic tracheal allografts develop obliterative airway disease (OAD), a model of chronic rejection after human lung transplantation (tx). This model fails to account for graft behavior in its native milieu, adjacent to recipient airway tissues. To evaluate the role of the airway epithelium in OAD development, we adapted a murine orthotopic tracheal transplant model.
Methods: BALB/c tracheal allografts were transplanted orthotopically or heterotopically into C57BL/6 mice. Grafts were harvested at 14-60 days. Fluorescent mAb staining was done to determine the phenotype of the graft epithelium after orthotopic tx. Other orthotopic grafts harvested day 28 were re-transplanted heterotopically into Balb/c (syngeneic with original donor) or C57BL/6 mice (allogeneic with original donor) and harvested at day 28.
Results: Heterotopic tracheal allografts develop cellular infiltration and epithelial damage by day 14 and fibrotic obliteration by day 28. Orthotopic allografts have mild cellular infiltration, no fibrosis and an intact epithelium at 60 days. The presence of recipient derived epithelial cells was shown with immunofluorescent staining at day 14. Balb/c orthotopic allografts re-transplanted heterotopically into syngeneic Balb/c mice showed complete OAD development at day 28. Balb/c orthotopic allografts re-transplanted heterotopically into C57BL/6 mice had no OAD at day 28.
Conclusions: Repopulation of orthotopic tracheal allografts with recipient derived epithelium confers a protective effect against OAD. The fact that orthotopic grafts repopulated with allogeneic recipient epithelium reject when re-transplanted heterotopically into syngeneic mice indicates that immunologic injury to the epithelium is an early central event in OAD.