ID 113053
Author
Oishi, Hisashi University Health Network
Martinu, Tereza University Health Network
Hwang, David M. University Health Network
Sugihara, Junichi University Health Network
McKee, Trevor D. University Health Network
Bai, Xiaohui University Health Network
Guana, Zehong University Health Network
Lua, Christina University Health Network
Cho, Hae-Ra University Health Network
Juvet, Stephen University Health Network
Cypel, Marcelo University Health Network|University of Toronto
Keshavjee, Shaf University Health Network|University of Toronto
Liu, Mingyao University Health Network|University of Toronto
Keywords
innate immunity
Micro-CT
bronchiolitis obliterans
lymphatic aggregates
Th1/Th2 response
Content Type
Journal Article
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.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals, LLC
Volume
9
Issue
9
Start Page
8489
End Page
8501
Published Date
2018-01-03
Rights
Copyright: Yoshida et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences