| Project/Area Number |
07044225
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKATSU Kiyoshi Institute of Medical Science, University of Tokyo, Professor, 医科学研究所, 教授 (10107055)
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| Co-Investigator(Kenkyū-buntansha) |
SPRINGER Timothy Harvard University Medical School, Professor, 医学部, 教授
MELCHERS Fritz Basel Institute for Immunology, Director, 所長
KIKUCHI Yuji Institute of Medical Science, University of Tokyo, Research associate, 医科学研究所, 助手 (60262078)
KINASHI Tatsuo Institute of Medical Science, University of Tokyo, Research associate, 医科学研究所, 助手 (30202039)
TIMOTHY Spri ハーバード大学, 医学部, 教授
FRITZ Melche バーゼル免疫学研究所, 所長
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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 |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | cell surface receptors / adhesion molecules / cytokine receptors / IL-5 receptor / signal transduction / integrin / サイトカインレセプター / インターロイキン5 / レセプター型チロシンキナーゼ / IL-5Rα欠損マウス |
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| Research Abstract |
Although adhesion can be regulated by the expression of integrin and its igand, adhesion can be also mediated by integrin without any change of the expression level. This regulation of adhesion is called avidity modulation. Bone-marrow derived mast cells adhere to fibronectin via VLA-5 only stimulated with PMA,steel factor, or crosslinking with FceRI without any change of expression levels of VLA-5. Avidity modulation of integrin can be brought by either spatial redistribution of integrin molecules or a change of affinity for a ligand.
First we analyzed morphological changes and subcellulare localization of integrin VLA-5 with or without these stimuli. Without stimuli, VLA-5 were distributed as a cluster on the cell body. Stimulation with SLF and PMA,but not FceRI induced ruffle-like membrane structures and diffused distribution of VLA-5, which was located on both the cell body and ruffle-like structures. The affinity of VLA-5 against a 80 kD fibronectin fragment is beyond detectable levels in unstimulated mast cells. Stimulation with crosslinking of FceRI,but not with SLF or PMA increased the affinity of VLA-5. Therefore, SLF and PMA modulate mainly a spatial organization of VLA-5 molecules, while FceRI modulates the affinity of VLA-5 against fibronectin. These results suggest that spatial organization of VLA-5 on mast cells were differentially regulated with distinct stimuli.
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