Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants

Mikio Okazaki, Andrew E. Gelman, Jeremy R. Tietjens, Aida Richardson, Christopher G. Kornfeld, Howard J. Huang, Steven B. Richardson, Jiaming Lai, Joel R. Garbow, G. Alexander Patterson, Alexander S. Krupnick, Steven L. Brody, Daniel Kreisel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)625-630
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume37
Issue number6
DOIs
StatePublished - Dec 2007

Keywords

  • Airway epithelium
  • Bcl-2
  • Lung transplantation
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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