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Title: Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks
Authors: De Vleeschauwer, St├ęphanie ×
Jungraithmayr, Wolfgang
Wauters S., Shana
Willems, Stijn
Rinaldi, Manuela
Vaneylen, Annemie
Verleden, Stijn
Willems-Widyastuti, Anna
Bracke, Ken
Brusselle, Guy
Verbeken, Erik
Van Raemdonck, Dirk
Verleden, Geert
Vanaudenaerde, Bart #
Issue Date: 2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:1 pages:e29802
Article number: e29802
Abstract: Almost all animal models for chronic rejection (CR) after lung transplantation (LTx) fail to resemble the human situation. It was our attempt to develop a representative model of CR in mice. Orthotopic LTx was performed in allografts receiving daily immunosuppression with steroids and cyclosporine. Controls included isografts and mice only undergoing thoracotomy (SHAM). Allografts were sacrificed 2, 4, 6, 8, 10 or 12 weeks after LTx. Pulmonary function was measured repeatedly in the 12w allografts, isografts and SHAM mice. Histologically, all allografts demonstrated acute rejection (AR) around the blood vessels and airways two weeks after LTx. This decreased to 50-75% up to 10 weeks and was absent after 12 weeks. Obliterative bronchiolitis (OB) lesions were observed in 25-50% of the mice from 4-12 weeks. Isografts and lungs of SHAM mice were normal after 12 weeks. Pulmonary function measurements showed a decline in FEV(0.1), TLC and compliance in the allografts postoperatively (2 weeks) with a slow recovery over time. After this initial decline, lung function of allografts increased more than in isografts and SHAM mice indicating that pulmonary function measurement is not a good tool to diagnose CR in a mouse. We conclude that a true model for CR, with clear OB lesions in about one third of the animals, but without a decline in lung function, is possible. This model is an important step forward in the development of an ideal model for CR which will open new perspectives in unraveling CR pathogenesis and exploring new treatment options.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pneumology
× corresponding author
# (joint) last author

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