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.
Chen
Chang
C
Department of General Thoracic Surgery, Tongji University-Affiliated Shanghai Pulmonary Hospital, Shanghai, China.
Zhang
Yun-Zeng
YZ
Zheng
Hui
H
Xu
Bao-Bin
BB
Gao
Wen
W
D000818:Animals; D017209:Apoptosis; D001989:Bronchiolitis Obliterans / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D016040:Lung Transplantation / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000473:pathology / Q000648:ultrastructure; D014132:Trachea / Q000473:pathology / Q000637:transplantation* / Q000648:ultrastructure; D016042:Transplantation, Heterotopic / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000473:pathology
D016207:Cytokines