| Project/Area Number |
04671506
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Tohoku University |
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Principal Investigator |
YANAI Nobuaki Tohoku University Institute of Development, Aging and Cancer, Department of Cell Biology, Instructor, 加齢医学研究所, 助手 (80200525)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | erythropoiesis / erythrocyte / microenvironment / integrin / VLA-4 / VCAM-1 / c-Kit / stem cell factor / 赤芽球 / 造血微小環境 |
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| Research Abstract |
Adhesion molecules are required for differentiation and proliferation of erythroid progenitor cells in the erythropoietic microenvironment. We previously showed that erythroid progenitor cells are dependent on their direct adhesion to the stroma cells established from the erythropoietic organs. In this stroma dependent erythropoiesis, we examined the role of adhesion molecules and c-Kit (receptor of stem cell factor) by blocking antibodies. During these two years, we have revealed that direct cell-to-cell contact via integrin VLA-4 is required in addition to stem cell (SCF) and erythropoietin in erythropoietic microenvironment, and erythroid supportive stromal cells express stem cell factor and VCAM-1 (ligand for VLA-4). Whereas high level of expression of VCM-1 was detected in the stroma cells, the adhesion and development of the erythroid progenitor cells were partially inhibited by the blocking antibody against VCM-1. The stroma cells may support erythrogenesis by the adhesion through a new ligand molecules for VLA-4 in addition to VCAM-1. Then we have tried to identify such molecules by producing monoclonal antibodies against the erythroid suportive stroma cell line. We selected one monoclonal antibody giving specific staining t red pulp of spleen where erythroid cells are developing, and a new gene was cloned by this monoclonal antibody.
In another experiment, we have cloned many stromal cell lines from the bone marrow of temperature sensitive SV40 T-antigen harboring transgenic mice. Among these stromal cell lines, we found monocyte supportive and granulocyte supportive stromal cell lines except for erytyroid supportive stroma cell lines.
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