Project/Area Number |
13557160
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
病態科学系歯学(含放射線系歯学)
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
UMEHARA Hisanori KYOTO UNIV., ASS.PRO, 医学研究科, 助教授 (70247881)
|
Co-Investigator(Kenkyū-buntansha) |
IMAI Toshio KAN RESEARCH INST., director, カン研究所, 所長
MIMORI Tsuneyo KYOTO UNIV., PROF., 医学研究科, 教授 (10157589)
堂前 尚親 大阪歯科大学, 歯学部, 教授 (60115889)
|
Project Period (FY) |
2001 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | fractalkine / chemokine / NK cells / tumor cytotoxicity / adoptive immune therapy / endothelial cells / 細胞接着 / CD2 / IFN-γ / 細胞傷害 / 頭頸部腫瘍 / fractalkine / 血管傷害 |
Research Abstract |
For the improvement of adoptive immune therapy, we investigated the mechanisms of the major side effects, vascular leak syndrome and functional roles of membrane lipid rafts of NK cells. We found 1) After identification of the receptor for fractalkine, CX3CR1, we reported that CX3CR1 was expressed on CD 14+ monocytes, CD 16+ NK cells and CD8+ T cells. 2) Integrins and fractalkine synergistically enhanced cell adhesion. 3) Fractalkine enhanced cell adhesion and granular exocytosis of NK cells. Fractalkine expressed on activated endothelial cells caused NK cell lysis and vascular injury. 4) Fractalkine activated NK cells and produced IFN-gamma, which may mediate Th1-type immune response. 5) Membrane lipid rafts was involved in cytotoxicity of NK cells. 6) Sphingomyelin of the membrane was important for cellular activation and apoptosis. These results may provide the new insight for the improvement for adoptive immune therapy by reducing its side effects, vascular leak syndrome, and improved the efficacy of therapy.
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