Spectrum of chronic lung allograft pathology in a mouse minor-mismatched orthotopic lung transplant model. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Martinu, T., Oishi, H., Juvet, S. C., Cypel, M., Liu, M., Berry, G. J., Hwang, D. M., Keshavjee, S. 2018


Chronic lung allograft dysfunction (CLAD) is a fatal condition that limits survival after lung transplantation (LTx). The pathological hallmark of CLAD is obliterative bronchiolitis (OB). A subset of patients present with a more aggressive CLAD phenotype, called restrictive allograft syndrome (RAS), characterized by lung parenchymal fibrosis (PF). The mouse orthotopic single LTx model has proven relevant to the mechanistic study of allograft injury. The minor-alloantigen- mismatched strain combination using C57BL/10(B10) donors and C57BL/6(B6) recipients reportedly leads to OB. Recognizing that OB severity is a spectrum that may co-exist with other pathologies, including PF, we aimed to characterize and quantify pathologic features of CLAD in this model. Left LTx was performed in the following combinations: B10B6, B6B10, B6B6. Four weeks post-transplant, blinded pathologic semi-quantitative assessment showed that OB was present in 66% of B10B6 and 30% of B6B10 grafts. Most mice with OB also had PF with a pattern of pleuroparenchymal fibroelastosis, reminiscent of human RAS-related pathology. Grading of pathologic changes demonstrated variable severity of airway fibrosis, PF, acute rejection, vascular fibrosis and epithelial changes, similar to those seen in human CLAD. These assessments can make the murine LTx model a more useful tool for further mechanistic studies of CLAD pathogenesis. This article is protected by copyright. All rights reserved.

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