Suppression of the obliteration process by ventilation in a mouse orthotopic tracheal transplantation model.

Background: Obliterative airway disease (OAD) has been a major obstacle to long-term survival after lung or tracheal transplantations, but the role of airflow has not been examined in the orthotopic or the heterotopic tracheal transplantation models.
Methods: Sixty mice were assigned to two experimental groups. Two C57BL/6 tracheal segments were surgically prepared and then orthotopically transplanted into allogeneic BALB/c recipients. In group A mice, both segments were left patent, whereas in group B mice, one of the donor tracheas was occluded with a silk knot to obstruct airflow. Histology, quantitative OAD measurements, electron microscopy, immunohistochemical staining, and apoptosis measurement of the epithelium were performed.
Results: Gross examination at harvest showed patent lumens of all tracheal segments. Group A allografts (ventilating tracheas) showed a markedly higher proportion of ciliated epitheliums and less lymphocyte infiltration in the lamina propria, whereas the epithelium appeared metaplastic in group B, with a higher proportion of flattened attenuated epithelium and loss of the normal ciliate architecture. Quantitative morphometric measurements suggested more prominent OAD manifestations in the nonventilating allografts of group B than were present in group A, although recipient-derived epithelium was observed in all allografts under immunohistochemical staining. The apoptotic indexes of the epithelium were 12.1% in allografts with adequate ventilation (group A) and 66.2% in ventilation-occluded allotracheas (group B).
Conclusions: OAD severity and the epithelial repopulation process are closely related to the physiologic environment of airflow. Further research is warranted to explore the underlying mechanisms of this phenomenon.