title: Apoptosis of the Tracheal Epithelium Can Increase the Number of Recipient Bone Marrow-Derived Myofibroblasts in Allografts and Exacerbate Obliterative Bronchiolitis After Tracheal Transplantation in Mice.
abstract: The long-term outcome of lung transplantation is impeded by the development of obliterative bronchiolitis (OB). We sought to investigate the relationship between the apoptosis of tracheal epithelial cells and bone marrow-derived myofibroblasts in the process of OB.
  
  
  
  The mouse orthotopic tracheal transplant model was established. The allografts and syngrafts were harvested at 1, 2, 3, and 4 weeks after tracheal transplant. The percentage of tracheal lumen occlusion was assayed via histology and morphometry. Immunofluorescence staining was used to detect the apoptotic epithelial cells and recipient-derived myofibroblasts. The expression of SDF-1α and TGF-β and the infiltrations of CD4 and CD8 T cells in the grafts were detected using immunohistochemical staining.
  
  
  
  We found that there were more apoptotic epithelia in the allograft group than in the syngraft group and that the level of tracheal lumen occlusion was higher at different time points. Moreover, the increase in the apoptosis of the tracheal epithelium occurred earlier than that of occlusion of the tracheal lumen. There were more myofibroblasts derived from the recipient's bone marrow and more CD4 and CD8 T cells in the allografts. The expression of SDF-1α and TGF-β was higher in the epithelium from allografts than in those of the syngrafts.
  
  
  
  Our study indicated that the apoptotic tracheal epithelia in the OB model might increase the amount of myofibroblasts derived from the recipient's bone marrow. Therapeutic methods aimed at preventing apoptosis of the tracheal epithelium may improve the outcome of lung transplantation.
authors.affiliation: 1 Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2 Department of Integrative Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chuanxiao
authors.initials: C
authors.lastname: Wang
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Ke
authors.initials: K
authors.lastname: Jiang
authors.forename: Xinwei
authors.initials: X
authors.lastname: Qiao
authors.forename: Xiayi
authors.initials: X
authors.lastname: Zhang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Nie
mesh_terms: D064591:Allografts; D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D055745:Bronchioles / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D013997:Time Factors; D014132:Trachea / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014135:Tracheal Stenosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016212:Transforming Growth Factor beta