| Project/Area Number |
05454213
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
NAGATA Osaka 1st Department, Osaka Bioscience Institute, Head, 第一研究部, 研究部長 (70114428)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Hiroshi 1st Department, Scientist, 第一研究部, 研究員 (90260174)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1994: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | neutrophils / colony-stimulating factor / hemopoietic cells / cytokine / receptor / signal transduction / G-CSF / 顆粒球 / G‐CSF |
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| Research Abstract |
Neutrophils are produced from the stem cells in the bone marrow via various intermediate cells. Granulocyte colony-stimulating factor (G-CSF) is a cytokine which regulates the proliferation and differentiation of neutrophils. The G-CSF receptor (G-CSF-R) is a member of the hemopoietic growth factor receptor family. Using the cloned G-CSF receptor cDNA and myeloid leukemia cells, we tried to reconstitute the proliferation and differentiation of neutrophils. A G-CSF-R expression plasmid was introduced into various IL-3-dependent mouse myeloid precursor cells such as FDC-P1 and L-GM which normally do not respond to G-CSF.G-CSF stimulated proliferation of FDC-P1 transformants. Wheres, G-CSF stimulated proliferation, and induced neutrophilic differentiation of L-GM cells. Mutational analysis of the G-CSF-R indicated that about 80 aminoacid domain in the membrane-proximal part of the G-CSF-R is responsible for transducing proliferation signal, while both N-terminus and C-terminus part of the G-CSF-R cytoplasmic region are required for differentiation signal transduction. G-CSF but neither IL-3 nor GM-CSF induced the MPO (myeloperoxidase) gene expression in these transformants. Analyzes of the promoter of MPO gene identified a cis-regulatory element which respond to the signal from the G-CSF receptor. Two nuclear factors binding to the element were identified. One of them is specifically expressed in myeloid cells, and seems to be a positive regulator for MPO gene expression. The other factor is ubiquitously expressed, and seems to negatively regulate the MPO gene expression.
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