CD47 blockade reduces ischemia/reperfusion injury in murine heart transplantation and improves donor heart preservation.

CD47 CD47mAb Cold ischemia time Heart transplantation Ischemia-reperfusion injury

Journal

International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259

Informations de publication

Date de publication:
08 Apr 2024
Historique:
received: 25 01 2024
revised: 13 03 2024
accepted: 26 03 2024
medline: 11 4 2024
pubmed: 11 4 2024
entrez: 10 4 2024
Statut: aheadofprint

Résumé

Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts. We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h. At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers. The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.

Sections du résumé

BACKGROUND BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction. We hypothesized that blocking the CD47-TSP-1 system would attenuate ischemia-reperfusion injury in the transplanted heart and, thus, improve the preservation of donor hearts.
METHODS METHODS
We utilized a syngeneic mouse heart transplant model to assess the effect of CD47 monoclonal antibody (CD47mAb) to treat MIRI. Donor hearts were perfused with CD47mAb or an isotype-matched control immunoglobulin (IgG2a) and were implanted into the abdominal cavity of the recipients after being stored in histidine-tryptophan-ketoglutarate (HTK) solution at 4 °C for 4 h or 8 h.
RESULTS RESULTS
At both the 4-h and 8-h preservation time points, mice in the experimental group perfused with CD47mAb exhibited prolonged survival in the transplanted heart, reduced inflammatory response and oxidative stress, significantly decreased inflammatory cell infiltration, and fewer apoptosis-related biomarkers.
CONCLUSION CONCLUSIONS
The application of CD47mAb for the blocking of CD47 attenuates MIRI as well as improves the preservation and prognosis of the transplanted heart in a murine heart transplant model.

Identifiants

DOI: 10.1016/j.intimp.2024.111953 PMID: 38599097
pubmed: 38599097
pii: S1567-5769(24)00471-5
doi: 10.1016/j.intimp.2024.111953
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111953

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Guangyin Li (G)

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Key Laboratories of Myocardial Ischemia Mechanism and Treatment, Harbin Medical University, Ministry of Education, Harbin 150086, China.

Jianfeng Chen (J)

Laboratory Animal Center, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Zhuo Wang (Z)

Ultrasound Molecular Imaging Joint Laboratory of Heilongjiang Province (International Cooperation), Harbin 150086, China.

Song Kang (S)

Ultrasound Molecular Imaging Joint Laboratory of Heilongjiang Province (International Cooperation), Harbin 150086, China.

Yingying Liu (Y)

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Xin Ai (X)

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Chun Wang (C)

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

Shuangquan Jiang (S)

Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Ultrasound Molecular Imaging Joint Laboratory of Heilongjiang Province (International Cooperation), Harbin 150086, China. Electronic address: 23237003@qq.com.

Classifications MeSH