Study of the mechanisms of the induction of hyporesponsiveness by intraportal infusion of donor cells by using GFP rats
| Project/Area Number |
13671234
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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 |
General surgery
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MATSUOKA Junji Okayama University, Hospital, assistant, 医学部・歯学部附属病院, 助手 (30332795)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Eiji Jichi Medical School, Professor, 医学部, 教授 (00245044)
TANAKA Noriaki Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10127566)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | transplantation / Immunosuppression / intraportal injection / rat / small intestine / 小腸移植 / 門脈内注入 |
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| Research Abstract |
Experimental small intestinal transplantation (GFP rats as recipients, normal rats as donors) revealed the following, 1) Infiltrationg lymphocytes into the transplanted small intestine were mainly of recipient origin (75% on Day1 after transplantation and 98% on Day 3). 2) Infiltrating lymphocytes were revealed in the sub-mucosal tissue. 3) Immunosuppression using FK506 even with high dosage was not strong enough to prolong graft survival.
Further experiment using GFP splenocytes and GFP bone marrow cells to perform intra portal and intravenous injections, the following was revealed. 1) Cells infused via the portal vein remain inside the liver for 24 hrs after infusion, and accumulate into the spleen. 2) Venous injection of GFP cells showed less accumulation to the liver in comparison with portal injection. 3) Cells accumulated into the spleen remained morpfologically intact in the spleen 7days after the injection. 4) GFP cells were revealed to exist inside the thymus, however the popul
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ation was not large. 5) There was no accumulation of GFP cells in the bone marrow.
The above observation suggests that spleen plays an important role in the induction of hyporesponsiveness by the portal injection of donor cells. The difference between venous and portal injection was the amount of liver accumulation of the injected GFP cells. This result suggest the possibility of filtering the effective immunosuppressive cell population by the liver after portal injection.
The GFP cells in the spleen were speculated to modulate the mode of immune reactions because they remained for long time after injection. The removal of the spleen after the portal injection of donor cells cancelled the induction of hyporesponsiveness in the rat cardiac allograft model. This result strongly support the role of spleen in the induction of hyporesponsiveness.
This is the first observation that the importance of the spleen instead of the liver was clearly indicated in the induction of hyporesponsiveness by intraportal injection of donor cells The analysis of the surface markers will bring more detailed information. Less
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Report
(3 results)
Research Products
(2 results)
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[Publications] N.Mitsuoka, T.Yagi, Y.Morimoto, M.Inagaki, H.Sadamori, H.Iwagaki, A.Nakao, D.J.Sun, M.Yamamura, J.Liu, H.Matsuda, J.Matsuoka, N.Tanaka: "Cytokinic Character of Graft Infiltrate Versus Peripheral Blood Lymphocytes During Calcineurin Inhibitor-Resistant Small Bowel Transplantation in Rats."Transplantation Proceedings. 35. 562-563 (2003)
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