| Project/Area Number |
10470210
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
HARADA Mine Okayama University Medical School, Professor, 医学部, 教授 (00019621)
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| Co-Investigator(Kenkyū-buntansha) |
SHINAGAWA Katsuji Okayama University Medical School, Assistant, 医学部・附属病院, 助手 (00273988)
ISHIMARU Fumihiko Okayama University Medical School, Assistant, 医学部・附属病院, 助手 (50284097)
KIURA Katsuyuki Okayama University Medical School, Lecturer, 医学部・附属病院, 講師 (10243502)
TAKENAKA Katsuto Okayama University Medical School, Assistant, 医学部・附属病院, 助手 (30301295)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Keywords | Hematopoietic stem cell / Peripheral blood stem cell / Cytokine / G-CSF / Mobilization / T cell modulation / Natural killer cell / GVHD / 同種末梢血幹細胞移植 / VLA-4 / 急性GVHD / IFN-γ / IL-4 / 単球 / CFU-GM / 末梢血幹細胞移植 / CD34 / TNF-α / インターフェロンγ / IL-10 |
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| Research Abstract |
Peripheral blood mononuclear cells(PBMNC)were obtained from healthy donors who received G-CSF for mobilization of peripheral blood stem cells(PBSC). Proliferative responses of nonadherent PBMNC to alloantigen and mitogen stimulation decreased after G-CSF administration compared to those before G-CSF administration. Furthemore, production of IL-4 and IFN-γ also decreased. When monocytes from PBSC donors were cultured with LPS, concentrations of TNF-α and IL-10 in their culture supernatants were significantly lower after G-CSF administration than those before G-CSF administration. Their activity of antigen presentation and NK cell activity also decreased after G-CSF administration. Thus, G-CSF gave rise to suppressive effects on functions of immunocompetent cells.
In an attempt to elucidate a mechanism of PBSC mobilization, roles of angiogenesis factors were investigated. VEGF concentrations in plasma and serum were significantly increased in PBSC donors after G-CSF administration, while bFGF concentrations did not show significant changes. Therefore, angiogenesis factors may be actively involved in PBSC mobilization.
Poor mobilization was observed in approximately 20% of healthy donors. Their serum levels of lactic dehydroge nose and C-reactive protein, and counts of circulating immature cells were significantly lower than those of normal mobilization. In addition, counts of circulating CD34-positive cells before G-CSF administration were lower in poor mobilization. Accordingly, mobilizing effects of G-CSF were different in donors of poor mobilization.
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