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

抄録

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.

収録刊行物

• Oncotarget

  Oncotarget 9 (9), 8489-8501, 2018-01-03

  Impact Journals, LLC

キーワード

• innate immunity
• Micro-CT
• bronchiolitis obliterans
• lymphatic aggregates
• Th1/Th2 response

詳細情報

• CRID: 1050001337992852224
• NII論文ID: 120006576959
• ISSN: 19492553
• Web Site: http://repo.lib.tokushima-u.ac.jp/113053
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles