1994 Fiscal Year Final Research Report Summary
Proliferation and differentiation of neutrophils
| Project/Area Number |
05454213
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | Osaka Bioscience Institute |
|---|
Principal Investigator |
NAGATA Osaka 1st Department, Osaka Bioscience Institute, Head, 第一研究部, 研究部長 (70114428)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Hiroshi 1st Department, Scientist, 第一研究部, 研究員 (90260174)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Keywords | neutrophils / colony-stimulating factor / hemopoietic cells / cytokine / receptor / signal transduction / G-CSF |
|---|
| 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.
|
-
-
-
-
-
-
-
-
-
-
-
[Publications] Ito, N., Seto, Y., Brannan, C.I., Copeland, N.G., Jenkins, N.A., Fukunaga, R.and Nagata, S.: "Structural analysis of the functional gene and pseudogene for the murine granulocyte colony-stimulating factor receptor." Eur.J.Biochem.220. 881-891 (1994)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Hiraoka, O., Anaguchi, H., Yamazaki, K., Fukunaga, R., Nagata, S.and Ota, Y.: "Ligand binding domain of granulocyte colony-stimulating factor receptor." J.Biol.Chem.269. 22412-22419 (1994)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Takahashi, T., Tanaka, M., Brannan, C.I., Jenkins, N.A., Copeland, N.G., Suda, T.and Nagata, S.: "Generalized Iymphoproliferative disease in mice, caused by a point mutation in the Fas ligand." Cell. 76. 969-976 (1994)
Description
「研究成果報告書概要(欧文)」より
-
