Chronic Airway Fibrosis in Orthotopic Mouse Lung Transplantation Models-An Experimental Reappraisal
BACKGROUND: Several mouse lung transplantation (Tx) models have been proposed for the study of chronic airway fibrosis (CAF), the most prevalent complication seen in human lung transplant recipients, termed chronic lung allograft dysfunction. Alternatively, it has been called for to establish an experimental animal model for restrictive allograft syndrome, another phenotype of chronic lung allograft dysfunction. However, these mouse transplant models exhibit significant heterogeneity in consistency and reproducibility. We therefore aimed at reevaluating current available models.
METHODS: Four different Tx combinations were used that manifest CAF: 2 minor antigen-mismatched Tx combinations (MINOR, donor: C57BL/10, recipient: C57BL/6J); or MINOR-N using recipient C57BL/6N, major histocompatibility antigen-mismatched immunosuppressed Tx (MAJOR, donor: BALB/c, recipient: C57BL/6J), and syngeneic Tx (donor and recipient: C57BL/6J) as control. The recipients were harvested and analyzed at week 8. Oxygenation, histology, reverse transcription polymerase chain reaction, and magnetic resonance imaging were performed to analyze outcome of those models.
RESULTS: The most prominent manifestation of CAF, thickest subepithelial fibrotic changes, worst oxygenation, and the most severe acute rejection were detected in the MAJOR group compared with all other (P < 0.05). Gene expressions of TNF-α and TGF-β1 were higher, and IL-10 was lower in the MAJOR group. Immunohistochemistry found pleuroparenchymal fibrotic change in both the MAJOR and MINOR-J groups.
CONCLUSIONS: We propose the major mismatch model under mild immunosuppression as the most suitable model for studying posttransplant CAF, and both the major and minor mismatch models for the restrictive phenotype.
| Errataetall: |
CommentIn: Transplantation. 2018 Feb;102(2):191-192. - PMID 29135860 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:102 |
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| Enthalten in: |
Transplantation - 102(2018), 2 vom: 01. Feb., Seite e49-e58 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yamada, Yoshito [VerfasserIn] |
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| Anmerkungen: |
Date Completed 13.09.2018 Date Revised 13.09.2018 published: Print CommentIn: Transplantation. 2018 Feb;102(2):191-192. - PMID 29135860 Citation Status MEDLINE |
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| doi: |
10.1097/TP.0000000000001917 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM274990199 |
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| 500 | |a CommentIn: Transplantation. 2018 Feb;102(2):191-192. - PMID 29135860 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Several mouse lung transplantation (Tx) models have been proposed for the study of chronic airway fibrosis (CAF), the most prevalent complication seen in human lung transplant recipients, termed chronic lung allograft dysfunction. Alternatively, it has been called for to establish an experimental animal model for restrictive allograft syndrome, another phenotype of chronic lung allograft dysfunction. However, these mouse transplant models exhibit significant heterogeneity in consistency and reproducibility. We therefore aimed at reevaluating current available models | ||
| 520 | |a METHODS: Four different Tx combinations were used that manifest CAF: 2 minor antigen-mismatched Tx combinations (MINOR, donor: C57BL/10, recipient: C57BL/6J); or MINOR-N using recipient C57BL/6N, major histocompatibility antigen-mismatched immunosuppressed Tx (MAJOR, donor: BALB/c, recipient: C57BL/6J), and syngeneic Tx (donor and recipient: C57BL/6J) as control. The recipients were harvested and analyzed at week 8. Oxygenation, histology, reverse transcription polymerase chain reaction, and magnetic resonance imaging were performed to analyze outcome of those models | ||
| 520 | |a RESULTS: The most prominent manifestation of CAF, thickest subepithelial fibrotic changes, worst oxygenation, and the most severe acute rejection were detected in the MAJOR group compared with all other (P < 0.05). Gene expressions of TNF-α and TGF-β1 were higher, and IL-10 was lower in the MAJOR group. Immunohistochemistry found pleuroparenchymal fibrotic change in both the MAJOR and MINOR-J groups | ||
| 520 | |a CONCLUSIONS: We propose the major mismatch model under mild immunosuppression as the most suitable model for studying posttransplant CAF, and both the major and minor mismatch models for the restrictive phenotype | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Windirsch, Kevin |e verfasserin |4 aut | |
| 700 | 1 | |a Dubs, Linus |e verfasserin |4 aut | |
| 700 | 1 | |a Kenkel, David |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Jae-Hwi |e verfasserin |4 aut | |
| 700 | 1 | |a Inci, Ilhan |e verfasserin |4 aut | |
| 700 | 1 | |a Boss, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Martinu, Tereza |e verfasserin |4 aut | |
| 700 | 1 | |a Vanaudenaerde, Bart |e verfasserin |4 aut | |
| 700 | 1 | |a Weder, Walter |e verfasserin |4 aut | |
| 700 | 1 | |a Jungraithmayr, Wolfgang |e verfasserin |4 aut | |
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