Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging
ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provi...
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Frontiers Media S.A.
2023-06-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/full |
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author | Yunjie Jin Yunjie Jin Peng Gao Lifei Liang Lifei Liang Yuhang Wang Jiawei Li Jiawei Li Jiyan Wang Jiyan Wang Jiangang Hou Cheng Yang Cheng Yang Cheng Yang Xiaolin Wang |
author_facet | Yunjie Jin Yunjie Jin Peng Gao Lifei Liang Lifei Liang Yuhang Wang Jiawei Li Jiawei Li Jiyan Wang Jiyan Wang Jiangang Hou Cheng Yang Cheng Yang Cheng Yang Xiaolin Wang |
author_sort | Yunjie Jin |
collection | DOAJ |
description | ObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation. |
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spelling | doaj.art-fceb71c963e94c07af099fe56d4711932023-06-26T10:24:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11641831164183Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imagingYunjie Jin0Yunjie Jin1Peng Gao2Lifei Liang3Lifei Liang4Yuhang Wang5Jiawei Li6Jiawei Li7Jiyan Wang8Jiyan Wang9Jiangang Hou10Cheng Yang11Cheng Yang12Cheng Yang13Xiaolin Wang14Shanghai Institute of Medical Imaging, Shanghai, ChinaDepartment of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaZhangjiang Institute of Fudan University, Shanghai, ChinaShanghai Institute of Medical Imaging, Shanghai, ChinaObjectiveEndomyocardial biopsy is the gold standard method for the diagnosis of cardiac allograft rejection. However, it causes damage to the heart. In this study, we developed a noninvasive method for quantification of granzyme B (GzB) in vivo by targeted ultrasound imaging, which detects and provides quantitative information for specific molecules, for acute rejection assessment in a murine cardiac transplantation model.MethodsMicrobubbles bearing anti-GzB antibodies (MBGzb) or isotype antibodies (MBcon) were prepared. Hearts were transplanted from C57BL/6J (allogeneic) or C3H (syngeneic) donors to C3H recipients. Target ultrasound imaging was performed on Days 2 and 5 post-transplantations. A pathologic assessment was performed. The expression of granzyme B and IL-6 in the heart was detected by Western blotting.ResultsAfter MB injection, we observed and collected data at 3 and 6 min before and after the flash pulse. Quantitative analysis revealed that the reduction in peak intensity was significantly higher in the allogeneic MBGzb group than in the allogeneic MBcon group and the isogeneic MBcon group at PODs 2 and 5. In the allogeneic groups, granzyme B and IL-6 expression levels were higher than those in the isogeneic group. In addition, more CD8 T cells and neutrophils were observed in the allogeneic groups.ConclusionUltrasound molecular imaging of granzyme B can be used as a noninvasive method for acute rejection detection after cardiac transplantation.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/fullcardiac transplantationultrasound imagingrejectioncontrast enhanced ultrasound (CEUS)granzyme B (GzmB) |
spellingShingle | Yunjie Jin Yunjie Jin Peng Gao Lifei Liang Lifei Liang Yuhang Wang Jiawei Li Jiawei Li Jiyan Wang Jiyan Wang Jiangang Hou Cheng Yang Cheng Yang Cheng Yang Xiaolin Wang Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging Frontiers in Immunology cardiac transplantation ultrasound imaging rejection contrast enhanced ultrasound (CEUS) granzyme B (GzmB) |
title | Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging |
title_full | Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging |
title_fullStr | Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging |
title_full_unstemmed | Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging |
title_short | Noninvasive quantification of granzyme B in cardiac allograft rejection using targeted ultrasound imaging |
title_sort | noninvasive quantification of granzyme b in cardiac allograft rejection using targeted ultrasound imaging |
topic | cardiac transplantation ultrasound imaging rejection contrast enhanced ultrasound (CEUS) granzyme B (GzmB) |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1164183/full |
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