Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks.
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....
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2012
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oai:doaj.org-article:a00fb88bf8524eb59e6a4b986d06d7dd2021-11-18T07:30:45ZChronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks.1932-620310.1371/journal.pone.0029802https://doaj.org/article/a00fb88bf8524eb59e6a4b986d06d7dd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22238655/?tool=EBIhttps://doaj.org/toc/1932-6203Almost 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.Stéphanie De VleeschauwerWolfgang JungraithmayrShana WautersStijn WillemsManuela RinaldiAnnemie VaneylenStijn VerledenAnna Willems-WidyastutiKen BrackeGuy BrusselleErik VerbekenDirk Van RaemdonckGeert VerledenBart VanaudenaerdePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29802 (2012) |
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Medicine R Science Q Stéphanie De Vleeschauwer Wolfgang Jungraithmayr Shana Wauters Stijn Willems Manuela Rinaldi Annemie Vaneylen Stijn Verleden Anna Willems-Widyastuti Ken Bracke Guy Brusselle Erik Verbeken Dirk Van Raemdonck Geert Verleden Bart Vanaudenaerde Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| description |
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. |
| format |
article |
| author |
Stéphanie De Vleeschauwer Wolfgang Jungraithmayr Shana Wauters Stijn Willems Manuela Rinaldi Annemie Vaneylen Stijn Verleden Anna Willems-Widyastuti Ken Bracke Guy Brusselle Erik Verbeken Dirk Van Raemdonck Geert Verleden Bart Vanaudenaerde |
| author_facet |
Stéphanie De Vleeschauwer Wolfgang Jungraithmayr Shana Wauters Stijn Willems Manuela Rinaldi Annemie Vaneylen Stijn Verleden Anna Willems-Widyastuti Ken Bracke Guy Brusselle Erik Verbeken Dirk Van Raemdonck Geert Verleden Bart Vanaudenaerde |
| author_sort |
Stéphanie De Vleeschauwer |
| title |
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| title_short |
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| title_full |
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| title_fullStr |
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| title_full_unstemmed |
Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. |
| title_sort |
chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine bos model and its drawbacks. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/a00fb88bf8524eb59e6a4b986d06d7dd |
| work_keys_str_mv |
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