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Mol. Cells 2012; 33(1): 79-86

Published online January 3, 2012

https://doi.org/10.1007/s10059-012-2228-y

© The Korean Society for Molecular and Cellular Biology

In Vivo Imaging of Differences in Early Donor Cell Proliferation in Graft-Versus-Host Disease Hosts with Different Pre-Conditioning Doses

Myung Geun Song1,2,3,9, Bora Kang4,9, Ji Yeong Jeon4, Jun Chang5, Seungbok Lee6, Chang-Ki Min7, Hyewon Youn2,3,8,*, and Eun Young Choi4,*

1Department of Tumor Biology, Seoul National University College of Medicine, Seoul 110-799, Korea, 2Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea, 3Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea, 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea, 5Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea, 6Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 7Department of Internal Medicine, The Catholic University of Korea College of Medicine, St. Mary’s Hospital, Seoul 137-701, Korea, 8Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul 110-799, Korea, 9These authors contributed equally to this work.

Correspondence to : *Correspondence: ncpaek@snu.ac.kr

Received: October 7, 2011; Revised: October 18, 2011; Accepted: October 19, 2011

Abstract

Graft-versus-host disease (GVHD) results from immune-mediated attacks on recipient tissues by donor-originated cells through the recognition of incompatible antigens expressed on host cells. The pre-conditioning irradiation dose is a risk factor influencing GVHD severity. In this study, using newly generated luciferase transgenic mice on a B6 background (B6.LucTg) as bone marrow and splenocyte donors, we explored the effects of irradiation doses on donor cell dynamics in major histocompatibility complex (MHC)-matched allogeneic GVHD hosts via bioluminescence imaging (BLI). Results from BLI of GVHD hosts showed higher emission intensities of luminescence signals from hosts irradiated with 900 cGy as compared with those irradiated with 400 cGy. In particular, BLI signals from target organs, such as the spleen, liver, and lung, and several different lymph nodes fluctuated with similar time kinetics soon after transplantation, reflecting the synchronous proliferation of donor cells in the different organs in hosts irradiated with 900 cGy. The kinetic curves of the BLI signals were not synchronized between the target organs and the secondary organs in hosts irradiated with 400 cGy. These results demonstrate that pre-condi-tioning doses influence the kinetics and degree of proliferation in the target organs soon after transplantation. The results from this study are the first describing donor cell dynam-ics in MHC-matched allogeneic GVHD hosts and the influence of irradiation doses on proliferation dynamics, and will provide spatiotemporal information to help understand GVHD pathophysiology.

Keywords bioluminescence imaging, graft-versus-host disease, irradiation dose, luciferase, transgenic mouse

Article

Research Article

Mol. Cells 2012; 33(1): 79-86

Published online January 31, 2012 https://doi.org/10.1007/s10059-012-2228-y

Copyright © The Korean Society for Molecular and Cellular Biology.

In Vivo Imaging of Differences in Early Donor Cell Proliferation in Graft-Versus-Host Disease Hosts with Different Pre-Conditioning Doses

Myung Geun Song1,2,3,9, Bora Kang4,9, Ji Yeong Jeon4, Jun Chang5, Seungbok Lee6, Chang-Ki Min7, Hyewon Youn2,3,8,*, and Eun Young Choi4,*

1Department of Tumor Biology, Seoul National University College of Medicine, Seoul 110-799, Korea, 2Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea, 3Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea, 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea, 5Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea, 6Department of Cell and Developmental Biology, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 7Department of Internal Medicine, The Catholic University of Korea College of Medicine, St. Mary’s Hospital, Seoul 137-701, Korea, 8Cancer Imaging Center, Seoul National University Cancer Hospital, Seoul 110-799, Korea, 9These authors contributed equally to this work.

Correspondence to:*Correspondence: ncpaek@snu.ac.kr

Received: October 7, 2011; Revised: October 18, 2011; Accepted: October 19, 2011

Abstract

Graft-versus-host disease (GVHD) results from immune-mediated attacks on recipient tissues by donor-originated cells through the recognition of incompatible antigens expressed on host cells. The pre-conditioning irradiation dose is a risk factor influencing GVHD severity. In this study, using newly generated luciferase transgenic mice on a B6 background (B6.LucTg) as bone marrow and splenocyte donors, we explored the effects of irradiation doses on donor cell dynamics in major histocompatibility complex (MHC)-matched allogeneic GVHD hosts via bioluminescence imaging (BLI). Results from BLI of GVHD hosts showed higher emission intensities of luminescence signals from hosts irradiated with 900 cGy as compared with those irradiated with 400 cGy. In particular, BLI signals from target organs, such as the spleen, liver, and lung, and several different lymph nodes fluctuated with similar time kinetics soon after transplantation, reflecting the synchronous proliferation of donor cells in the different organs in hosts irradiated with 900 cGy. The kinetic curves of the BLI signals were not synchronized between the target organs and the secondary organs in hosts irradiated with 400 cGy. These results demonstrate that pre-condi-tioning doses influence the kinetics and degree of proliferation in the target organs soon after transplantation. The results from this study are the first describing donor cell dynam-ics in MHC-matched allogeneic GVHD hosts and the influence of irradiation doses on proliferation dynamics, and will provide spatiotemporal information to help understand GVHD pathophysiology.

Keywords: bioluminescence imaging, graft-versus-host disease, irradiation dose, luciferase, transgenic mouse

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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