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

Oncotarget
Mitsuteru YoshidaMingyao Liu

Abstract

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...Continue Reading

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Citations

Jul 30, 2019·Frontiers in Immunology·Thiago Henrique Caldeira de OliveiraFlávio Almeida Amaral
Nov 20, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Changhai LiCarl Atkinson
Oct 31, 2020·The European Respiratory Journal·Cristina BaciuMingyao Liu
Jul 4, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Liran LevyTereza Martinu

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Methods Mentioned

BETA
PCR
genotyping

Software Mentioned

Definiens Tissue Studio
ImageJ
MicroView
Definiens TissueStudio
Graph Pad
Prism

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