Orthotopic tracheal allografts undergo reepithelialization with recipient-derived epithelium.
BACKGROUND
While the rejection of heterotopic tracheal allografts is characterized by complete airway obliteration, the rejection of orthotopic allografts leads to airway edema and cellular infiltrate of the lamina propria, but is not associated with obliteration. We hypothesized that orthotopic tracheal allografts undergo reepithelialization with recipient-derived mucosa and that this process prevents airway obliteration.


METHODS
Thirty mice were randomly assigned to 6 experimental groups. BALB/c donor tracheal segments were transplanted orthotopically or heterotopically into syngeneic BALB/c or major histocompatability mismatched allogeneic C57BL/6 recipients. Recipients of allogeneic grafts were divided into a nonimmunosuppression group and an immunosuppression group (cyclosporine, 7 mg/kg per day). Twenty-one days after transplantation, histological assessment, immunohistochemistry for CD4 and CD8 lymphocyte infiltration and major histocompatibility-specific immunohistochemistry were performed on the grafts to assess rejection and donor or recipient origin of tissue.


RESULTS
Untreated heterotopic allografts underwent complete airway obliteration by day 21. This response was prevented with cyclosporine immunosuppression. Untreated orthotopic allografts, however, demonstrated edema and lymphocytic infiltrate of the lamina propria resulting in clinical stridor without airway obliteration. Immunosuppressed orthotopic allografts did not develop edema or infiltrate of the lamina propria and consequently stridor did not occur. Immunohistochemical analysis demonstrated migration of recipient-derived mucosa into the donor allograft segment in both the untreated and treated orthotopic groups.


CONCLUSIONS
Airway obliteration characteristic of rejecting heterotopic tracheal allografts does not occur in the orthotopic allografts. Migration of recipient mucosa into the donor allograft appears to prevent airway obliteration in the orthotopic allografts. These findings suggest that the orthotopic tracheal transplantation model more accurately represents the biological behavior of clinical tracheal allografts than the traditional heterotopic model.
Genden
Eric M
EM
Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA. eric.genden@mssm.edu
Iskander
Andrew J
AJ
Bromberg
Jonathan S
JS
Mayer
Lloyd
L
D000402:Airway Obstruction / Q000473:pathology; D000818:Animals; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008953:Models, Anatomic; D011897:Random Allocation; D014132:Trachea / Q000637:transplantation*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous