Induction of microchimerisim and attenuation of chronic rejection in lung transplantation
| Project/Area Number |
11671327
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | The university of Tokushima |
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Principal Investigator |
SHOJI Sakiyama Medicine, 2nd Dept of Surg, The university of Tokushima, 医学部, 助手 (60291986)
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| Co-Investigator(Kenkyū-buntansha) |
KONDO Kazuya Medicine, 2nd Dept of Surg, The university of Tokushima, Lecturer, 医学部, 講師 (10263815)
MONDEN Yasumasa Medicine, 2nd Dept of Surg, The university of Tokushima, Professor, 医学部, 教授 (60028628)
谷田 信行 徳島大学, 医学部・附属病院, 助手 (20311821)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | lung transplantation / rat / chronic rejection / ラット同所性肺移植 / 胸腺内移植 / ドナー骨髄細胞 / 拒絶反応 |
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| Research Abstract |
In the rat lung transplantation model with no immuno-suppression, rejection of BN (RT1^n) lungs in LWE (RT1^1) recipients occurs faster than that of LEW lungs in BN.BN lungs in LEW are indefinitely accepted with a short course of cyclosporin administration after transplantation (25mg/kg, i.m., day 2 and day 3), and show late air way changes consisting of epithelial ulceration with submucosal lymphocytic infiltration. These changes are shown in the large bronchi. According to the immunological status of recipient rats with long-term surviving allografts, we were able to show that the spleen cells from recipient rats were able to respond to donor antigens in MLR and F1 GVH assay. In addition, donor type skin grafts implanted to the recipient rats induced the rejection of lung grafts that had been accepted for 6 month by recipients.
In this model, we tried to induce the complete tolerance with thymic inoculation of donor cells. This was done to that show the attenuation of the bronchial pathological changes causes chronic rejection. However, the expected results were not shown using this model. Perhaps by modifying immunosuppression and recipient-donor combination, we can create a more sever chronic rejection model that will help us verify our hypothesis.
Accompanying with this experiment, we found an interesting new phenomenon in this rat transplantation model. In acute rejection without immunosuppression, BN lungs in LEW were rejected more strongly than LEW lungs in BN.However, a short course CsA treatment reversed this relationship. That is, BN lungs in LEW were indefinitely accepted, while LEW lungs in BN were rejected within 21 days in animals treated with CsA.We postulate that the timing of immunosupression cause such a paradoxical phenomenon. In LEW-to-BN combination (lower responder combination), the timing of CsA treatment on days 2 and 3 after transplantation is perhaps early to introduce the hypo-alloreactive status.
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Report
(3 results)
Research Products
(2 results)
