2002 Fiscal Year Final Research Report Summary
Analysis of CS5 co-receptor molecule that specifically inhibits chemotaxis of polymorphonuclear leukocytes
| Project/Area Number |
12470058
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kumamoto University |
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Principal Investigator |
YAMAMOTO Tetsuro Kumamoto University, Graduate School of Medical Science, Professor, 大学院・医学研究科, 教授 (60112405)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Norikazu Kyushu Institute of Technology, Faculty of Engineering, Professor, 工学部, 教授 (40145165)
NAKAYAMA Hitoshi Kumamoto University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (70088863)
SEMBA Umeko Kumamoto University, School of Medicine, Faculty Member, 医学部附属病院, 助手 (50109691)
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| Project Period (FY) |
2000 – 2002
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| Keywords | ribosomal protein / leukocyte / chemotaxis / C5a receptor / apoptosis / transglutaminase / inflammation / antagonist |
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| Research Abstract |
The cross-linked dimer of RP S19 attracted monocytes as an agonist of C5a receptor. On the other hand, the same molecule inhibited the chemotaxis of polymorphonuclear leukocytes (PMN) as an antagonist of the C5a receptor. We initially identified the ligand moieties of the RP S19 dimer to the C5a receptor of monocytes. The RP S19 dimer bound to the C5a receptor by a two-step mechanism. The first ligand and second ligand moieties were identified to be-Lys41-His42-Lys43- and -Leu131-Asp132-Arg133-, respectively.
Next, we identified a switch moiety on the RPS19 dimer molecule, which converted the agonist function to the antagonist in the C5a receptor-mediated chemotaxis of PMN. The switch moiety was identified to be from Ile134 to Lys144 (IAGQVAAANKK), which was present following to the second ligand moiety.
We made a hypothesis that PMN had a molecule near the C5a receptor, which negatively regulated the intracellular signaling raised by the activated C5a receptor. Then we have been trying to identify the co-receptor molecule. We have prepared a subtraction cDNA library between a PMN cDNA pool and a monocyte cDNA pool. We have tried to prepare an analogue peptide with the second ligand moiety and the switch moiety that bore a fluorescence-labeled photosensitive chemical modifier. However, we have not succeeded to identify the co-receptor molecule of the PMN C5a receptor.
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