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Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks

Stephanie De Vleeschauwer, Wolfgang Jungraithmayr, Shana Wauters, Stijn Willems, Manuela Rinaldi, Annemie Vaneylen, Stijn Verleden, Anna Willems-Widyastuti, Ken Bracke UGent and Guy Brusselle UGent, et al. (2012) PLOS ONE. 7(1).
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 FEV0.1, 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
OBLITERATIVE BRONCHIOLITIS, MOUSE MODEL, ANIMAL-MODEL, INJURY, ALLOGRAFT
journal title
PLOS ONE
PLoS One
volume
7
issue
1
article_number
e29802
pages
9 pages
Web of Science type
Article
Web of Science id
000301188800039
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.73 (2012)
JCR rank
7/56 (2012)
JCR quartile
1 (2012)
ISSN
1932-6203
DOI
10.1371/journal.pone.0029802
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
2963466
handle
http://hdl.handle.net/1854/LU-2963466
date created
2012-07-19 15:35:21
date last changed
2012-08-03 14:01:45
@article{2963466,
  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 FEV0.1, 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.},
  articleno    = {e29802},
  author       = {De Vleeschauwer, Stephanie and Jungraithmayr, Wolfgang and Wauters, Shana and Willems, Stijn and Rinaldi, Manuela and Vaneylen, Annemie and Verleden, Stijn and Willems-Widyastuti, Anna and Bracke, Ken and Brusselle, Guy and Verbeken, Erik and Van Raemdonck, Dirk and Verleden, Geert and Vanaudenaerde, Bart},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {OBLITERATIVE BRONCHIOLITIS,MOUSE MODEL,ANIMAL-MODEL,INJURY,ALLOGRAFT},
  language     = {eng},
  number       = {1},
  pages        = {9},
  title        = {Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks},
  url          = {http://dx.doi.org/10.1371/journal.pone.0029802},
  volume       = {7},
  year         = {2012},
}

Chicago
De Vleeschauwer, Stephanie, Wolfgang Jungraithmayr, Shana Wauters, Stijn Willems, Manuela Rinaldi, Annemie Vaneylen, Stijn Verleden, et al. 2012. “Chronic Rejection Pathology After Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks.” Plos One 7 (1).
APA
De Vleeschauwer, S., Jungraithmayr, W., Wauters, S., Willems, S., Rinaldi, M., Vaneylen, A., Verleden, S., et al. (2012). Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. PLOS ONE, 7(1).
Vancouver
1.
De Vleeschauwer S, Jungraithmayr W, Wauters S, Willems S, Rinaldi M, Vaneylen A, et al. Chronic rejection pathology after orthotopic lung transplantation in mice: the development of a murine BOS model and its drawbacks. PLOS ONE. 2012;7(1).
MLA
De Vleeschauwer, Stephanie, Wolfgang Jungraithmayr, Shana Wauters, et al. “Chronic Rejection Pathology After Orthotopic Lung Transplantation in Mice: The Development of a Murine BOS Model and Its Drawbacks.” PLOS ONE 7.1 (2012): n. pag. Print.