| Project/Area Number |
11671020
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Occupational and Environmental Health |
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Principal Investigator |
MISAGO Masahiro UOEH School of Health Sciences, Associate Prof., 産業保健学部, 助教授 (30157474)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKADA Junichi UOEH School of Medicine, Associate Prof., 医学部, 助教授 (20227367)
江藤 澄哉 産業医科大学, 医学部, 教授 (90010347)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Asn-linked glycan / neutrophil maturation / deoxynojirimycin / swainsonine / G-CSF receptor |
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| Research Abstract |
The N-glycan inhibitors such as swainsonine and N-butyldeoxynojirimycin (NB-DN) lead to the biosynthesis of the incomplete N-linked oligosaccharide. The effects of these inhibitors on granulopoiesis was investigated using human bone marrow cells in vitro containing granulocyte colony-stimulating factor (G-CSF). The addition of the inhibitors led to the decrease in the number of mature neutrophils. Swainsonine did not induce apoptosis, but NB-DNJ induced considerable apoptosis. This result indicated that the decrease of mature neutrophils by swainsonine was not because of cell degeneration but the suppression of maturation from myelocytes into neutrophils. In the case of NB-DNJ, it was thought to be because of both apoptosis and maturation suppression. The inhibitors also suppressed the expressions of mRNAs of CCAAT/enhancer binding protein epsilon (C/EBPε) and G-CSF receptor as markers of terminal neutrophil maturation. Furthermore, the effect of NB-DNJ was investigated using all trans retinoic acid (ATRA)-stimulated HL-60 cells as the model of neutrophil differentiation. NB-DNJ suppressed the differentiation of HL-60 and the expression of G-CSF receptor mRNA. In this study, it has been elucidated that the inhibitors of N-linked oligosaccharide synthesis leads to the suppression of terminal neutrophil maturation.
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