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Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model

Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recip...

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Autores principales: Yoshida, Mitsuteru, Oishi, Hisashi, Martinu, Tereza, Hwang, David M., Takizawa, Hiromitsu, Sugihara, Junichi, McKee, Trevor D., Bai, Xiaohui, Guana, Zehong, Lua, Christina, Cho, Hae-Ra, Juvet, Stephen, Cypel, Marcelo, Keshavjee, Shaf, Liu, Mingyao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823599/
https://www.ncbi.nlm.nih.gov/pubmed/29492210
http://dx.doi.org/10.18632/oncotarget.23902
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author Yoshida, Mitsuteru
Oishi, Hisashi
Martinu, Tereza
Hwang, David M.
Takizawa, Hiromitsu
Sugihara, Junichi
McKee, Trevor D.
Bai, Xiaohui
Guana, Zehong
Lua, Christina
Cho, Hae-Ra
Juvet, Stephen
Cypel, Marcelo
Keshavjee, Shaf
Liu, Mingyao
author_facet Yoshida, Mitsuteru
Oishi, Hisashi
Martinu, Tereza
Hwang, David M.
Takizawa, Hiromitsu
Sugihara, Junichi
McKee, Trevor D.
Bai, Xiaohui
Guana, Zehong
Lua, Christina
Cho, Hae-Ra
Juvet, Stephen
Cypel, Marcelo
Keshavjee, Shaf
Liu, Mingyao
author_sort Yoshida, Mitsuteru
collection PubMed
description Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.
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spelling pubmed-58235992018-02-28 Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model Yoshida, Mitsuteru Oishi, Hisashi Martinu, Tereza Hwang, David M. Takizawa, Hiromitsu Sugihara, Junichi McKee, Trevor D. Bai, Xiaohui Guana, Zehong Lua, Christina Cho, Hae-Ra Juvet, Stephen Cypel, Marcelo Keshavjee, Shaf Liu, Mingyao Oncotarget Research Paper Chronic lung allograft dysfunction (CLAD) is a serious complication after lung transplantation and thought to represent chronic rejection. Increased expression of Pentraxin 3 (PTX3), an acute phase protein, was associated with worse outcome in lung transplant patients. To determine the role of recipient PTX3 in development of chronic rejection, we used a minor alloantigen-mismatched murine orthotopic single lung transplant model. Male C57BL/10 mice were used as donors. Male PTX3 knockout (KO) mice and their wild type (WT) littermates on 129/SvEv/C57BL6/J background were used as recipients. In KO recipients, 7/13 grafted lungs were consolidated without volume recovery on CT scan, while only 2/9 WT mice showed similar graft consolidation. For grafts where lung volume could be reliably analyzed by CT scan, the lung volume recovery was significantly reduced in KO mice compared to WT. Interstitial inflammation, parenchymal fibrosis and bronchiolitis obliterans scores were significantly higher in KO mice. Presence of myofibroblasts and lymphoid aggregation was significantly enhanced in the grafts of PTX3 KO recipients. Recipient PTX3 deficiency enhanced chronic rejection-like lesions by promoting a fibrotic process in the airways and lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored. Impact Journals LLC 2018-01-03 /pmc/articles/PMC5823599/ /pubmed/29492210 http://dx.doi.org/10.18632/oncotarget.23902 Text en Copyright: © 2018 Yoshida et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yoshida, Mitsuteru
Oishi, Hisashi
Martinu, Tereza
Hwang, David M.
Takizawa, Hiromitsu
Sugihara, Junichi
McKee, Trevor D.
Bai, Xiaohui
Guana, Zehong
Lua, Christina
Cho, Hae-Ra
Juvet, Stephen
Cypel, Marcelo
Keshavjee, Shaf
Liu, Mingyao
Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title_full Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title_fullStr Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title_full_unstemmed Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title_short Pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
title_sort pentraxin 3 deficiency enhances features of chronic rejection in a mouse orthotopic lung transplantation model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823599/
https://www.ncbi.nlm.nih.gov/pubmed/29492210
http://dx.doi.org/10.18632/oncotarget.23902
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