title: Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.
abstract: Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.
authors: Department of Surgery, and the Alvin J. Siteman Cancer Center, Washington University in St. Louis, St. Louis, Missouri, USA.
authors: Mikio
authors: M
authors: Okazaki
authors: Andrew E
authors: AE
authors: Gelman
authors: Jeremy R
authors: JR
authors: Tietjens
authors: Aida
authors: A
authors: Ibricevic
authors: Christopher G
authors: CG
authors: Kornfeld
authors: Howard J
authors: HJ
authors: Huang
authors: Steven B
authors: SB
authors: Richardson
authors: Jiaming
authors: J
authors: Lai
authors: Joel R
authors: JR
authors: Garbow
authors: G Alexander
authors: GA
authors: Patterson
authors: Alexander S
authors: AS
authors: Krupnick
authors: Steven L
authors: SL
authors: Brody
authors: Daniel
authors: D
authors: Kreisel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D006084:Graft Rejection; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016040:Lung Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D020545:Respiratory Mucosa / Q000098:blood supply* / Q000166:cytology* / Q000473:pathology; D014132:Trachea / Q000637:transplantation; D014184:Transplantation, Homologous; D015854:Up-Regulation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
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