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

Mitsuteru Yoshida, Hisashi Oishi, Tereza Martinu, David M. Hwang, Hiromitsu Takizawa, Junichi Sugihara, Trevor D. McKee, Xiaohui Bai, Zehong Guana, Christina Lua, Hae Ra Cho, Stephen Juvet, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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 lung parenchyma. The underlying mechanisms and potential protective role of exogenous PTX3 as a therapy should be further explored.

Original languageEnglish
Pages (from-to)8489-8501
Number of pages13
JournalOncotarget
Volume9
Issue number9
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • Bronchiolitis obliterans
  • Innate immunity
  • Lymphatic aggregates
  • Micro-CT
  • Th1/Th2 response

ASJC Scopus subject areas

  • Oncology

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