EPITHELIAL RE-GROWTH IS ASSOCIATED WITH INHIBITION OF OBLITERATIVE AIRWAY DISEASE IN ORTHOTOPIC TRACHEAL ALLOGRAFTS IN NON …
Background. Because epithelial cells are targets of alloimmune injury leading ultimately to
airway obliteration, we tested whether epithelial re-growth could prevent obliterative airway
disease (OAD) in orthotopic tracheal allografts. Methods. Brown Norway tracheal segments
were orthotopically transplanted into nonimmunosuppressed Lewis rats. Allografts were
removed on days 2–10 (n= 13), 30 (n= 4), and 60 (n= 5) for histology, computerized
morphometry (obliteration), and immunohistochemical detection of mononuclear cells …
airway obliteration, we tested whether epithelial re-growth could prevent obliterative airway
disease (OAD) in orthotopic tracheal allografts. Methods. Brown Norway tracheal segments
were orthotopically transplanted into nonimmunosuppressed Lewis rats. Allografts were
removed on days 2–10 (n= 13), 30 (n= 4), and 60 (n= 5) for histology, computerized
morphometry (obliteration), and immunohistochemical detection of mononuclear cells …
Abstract
Background.
Because epithelial cells are targets of alloimmune injury leading ultimately to airway obliteration, we tested whether epithelial re-growth could prevent obliterative airway disease (OAD) in orthotopic tracheal allografts.
Methods.
Brown Norway tracheal segments were orthotopically transplanted into nonimmunosuppressed Lewis rats. Allografts were removed on days 2–10 (n= 13), 30 (n= 4), and 60 (n= 5) for histology, computerized morphometry (obliteration), and immunohistochemical detection of mononuclear cells, smooth muscle α-actin, and tissue phenotype. Normal tracheas, host tracheas, and heterotopically transplanted allografts served as controls.
Results.
Orthotopic allografts removed on days 2–10 exhibited epithelial damage and re-growth and mononuclear cell infiltration. On days 30 and 60, partially ciliated cuboidal or attenuated epithelium completely covered the lumen. Although mononuclear cells declined, numerous T cells with a high CD4/CD8 ratio were found in the epithelium till day 60. Orthotopic allograft epithelium expressed donor phenotype on day 7, but recipient phenotype on days 30 and 60. Despite subepithelial α-actin positive myofibroblast proliferation, obliteration did not progress from day 7 to 30 and 60 (35, 30, and 33%, respectively). Although more than in normal or host tracheas, the obliteration in orthotopic allografts on days 30 and 60 was significantly less (P< 0.001) than in heterotopic allografts.
Conclusions.
We describe, for the first time, long-term patency of fully histoincompatible orthotopic tracheal allografts in nonimmunosuppressed rats. Despite acute alloimmune injury and induction of myofibroblast proliferation, epithelial re-growth from the host limited the progression of OAD, thus emphasizing the role of epithelium in the control of airway obliteration.
Lippincott Williams & Wilkins