| Project/Area Number |
07650945
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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 |
生物・生体工学
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| Research Institution | University of Tsukuba |
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Principal Investigator |
WANG Pi chao University of Tsukuba, Institution of Applied Biochemistry, Assistant Professor., 応用生物化学系, 講師 (80261775)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Masatoshi University of Tsukuba, Institution of Applied Biochemistry, Professor., 応用生物化学系, 教授 (50015781)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | CR1 (C3b receptor) / expression of receptor / anti DNA antibody / immune complex / renal glomerular cell / binding effect / cell therapy / 腎系球体細胞 / 捕捉・結合態 / 血液網内細胞 / 分化誘導因子 / C3bレセプター(CR1) |
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| Research Abstract |
This research discloses a novel concept different from the traditional aritificial kidney to cure the chronic renal disease, particularly the disease of SLE (systemic lupus erythematosus), which is regarded as an autoimmune disease casued by the existance of excessive amount of immune complex in the patients' serum. In this study, firstly the blood precusor cells were induced by cell-differentiation inducers to express the receptors, which can remove the immune complex by binding and/or phagocytosis. However, the inducers possessing high toxicity caused the cells dead and the desired receptors were unable to be expressed well in vitro. It was therefore that the expression mathod was changed into gene manupulation, and the experimental material was changed into renal glomerular epithelial cell which was related to the immune complex deposiition of kidney. The following results were obtained.
(1) A full lengh of human tonsil CR1 cDNA was successfully tranfected into normal rat renal glome
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rular epithelial cells, enabling the stable expression of CR1. Since the function of CR1 on the glomerular cells has not been clarified due to the failure expression in vitro, the contructed cell is considered useful experimenal system to clarify the receptor function.
(2) In order to clarify the correlation between CR1 and immunecomplex, DNA/anti DNA antibody immune complex was necessary. As anti DNA antibodies are not commercially available, hybridoma producing large amount of anti DNA antibody was contruced, and the desired DNA/anti DNA antibody was successfully prepared.
(3) The reaction between CR1 on the glomerular cells and immune complex revealed that CR1 can recognize and bind the immune complex, and the binding effect was mediated through complement C3b in the serum. The biological function of CR1 was clarified and the constructed cell is considered useful to remove the immune complex in vitro.
The further object of this research resides in the application of the constructed cells in cell therapy, and the induction of immune torleracne so as to feed the cells in vivo will be under investigation. Less
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