1996 Fiscal Year Final Research Report Summary
Development of anti-inflammatory drugs affecting functions of platelet adhesion molecules
| Project/Area Number |
06557134
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
医薬分子機能学
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| Research Institution | University of Tokyo |
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Principal Investigator |
TSUJI Tsutomu University of Tokyo, Associate Professor, 薬学部, 助教授 (00143503)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Jun-ishi Shimane Medical University, Professor, 医学部, 教授 (70173747)
YAMAMOTO Kazuo University of Tokyo, Assistant Professor, 薬学部, 助手 (20174782)
IMAI Yasuyuki University of Tokyo, Assistant Professor, 薬学部, 助手 (80160034)
IRIMURA Tatsuro University of Tokyo, Professor, 薬学部, 教授 (80092146)
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| Project Period (FY) |
1994 – 1996
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| Keywords | PLATELET / LEUKOCYTE / CELL ADHESION / INFLAMMATION / OXYGEN RADICAL / CYTOKINE / SELECTIN / CARBOHYDRATE CHAIN |
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| Research Abstract |
The purpose of this research project was the establishment of the basic concepts of the development of anti-inflammatory drugs affecting the cell adhesion between blood platelets and leukocytes. We got the following results.
(1) The screening methods of anti-platelet drugs modifying the functions of platelet adhesion molecules have been developped, where we utilized flow cytometry with fluorescence-labeled platelets and unlabeled leukocytes (2) Recombinant soluble P-selectin inhibited the superoxide anion production in leukocytes stimulated by formyl peptides or tumor necrosis factor-alpha (TNF-alpha). However, the soluble P-selectin had no effect on the oxygen radical production in these cells stimulated by phorbor ester or arachidonic acid. (3) The Neutrophils pretreated with interleukin-8 produced the oxygen radical in response to the soluble P-selectin. (4) When monocytes derived from peripheral blood were incubated in a plate which had been coated with P-selectin, these cells produced TNF-alpha. The optimal concentration of P-selectin for the coating of the plates was found to be 0.3 mug/ml. (5) When leukocytes were incubated with immobilized P-selectin, they peoduced superoxide anion and TNF-alpha. The distribution of P-selectin ligand, sialyl Lewis X carbohydrate, on these cells was examined by immuno-fluorescence microscopy. This carbohydrate epitopes were found to form a cluster at the bottom of the cell, which is the attachment site to the plate. This observation suggested the possible relationship between the leukocyte activation by P-selectin and the cluster formation of its carbohydrate ligand.
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