| Project/Area Number |
13670790
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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 |
Pediatrics
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| Research Institution | Shinshu University |
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Principal Investigator |
KOIKE Kenichi Shinshu University Graduate School of Medicine, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Associate Professor, 大学院・医学研究科, 助教授 (40143979)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIJO Takehiko Department of Pediatrics, Shinshu University School of Medicine, 医学部, 講師 (90262708)
AGEMATSU Kazunaga Shinshu University Graduate School of Medicine, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, 大学院・医学研究科, 助教授 (60262721)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | human mast cells / SCF / IL-9 / IL-6 / IL-4 / CD34^+ cells / stew cell factor / CD34陽性細胞 / ヒスタミン / インターロイキン6 / インターロイキン4 |
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| Research Abstract |
We examined the effects of IL-9 on human mast cell development from CD34^+ cord blood (CB) and peripheral blood (PB) cells in serum-deprived cultures. IL-9 apparently enhanced cell production under stimulation with stem cell factor (SCF) from CD34^+ CB cells. A great majority of the cultured cells grown with SCF+IL-9 became positive for tryptase at 4 wk. In methylcellulose cultures of CD34^+ CB cells, IL-9 increased both the number and size of mast cell colonies grown with SCF. Furthermore, SCF+IL-9 caused an exclusive expansion of mast cell colony-forming cells in 2-wk liquid culture of CD34+ CB cells, at a level markedly greater than for SCF alone. Clonal cell cultures and RT-PCR analysis showed that the target of SCF+IL-9 were the CD34^+CD38^+ CB cells rather than the CD34^+CD38^- CB cells. IL-9 neither augmented the SCF-dependent generation of progeny nor supported the survival of 6-wk cultured mast cells. Moreover, there was no difference in the appearance of tryptase^+ cells and
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histamine content in the cultured cells between SCF and SCF+IL-9. The addition of IL-9 increased numbers of mast cell colonies grown with SCF from CD34^+ PB cells in children with or without asthma. It is of interest that mast cell progenitors of asthmatic patients responded to SCF+IL-9 to a greater extent than those of normal controls. Taken together, IL-9 appears to act as a potent enhancer for the SCF-dependent growth of mast cell progenitors in humans, particularly asthmatic patients.
Next, we examined whether IL-6 exerts the stimulatory effects on the secretion of histamine from human mast cells triggered by crosslinking of the high affinity IgE receptor (FcεRI) with IgE and anti-IgE. As target cells, we used peripheral blood-derived cultured mast cells grown with SCF, because they were superior in FcεRIα expression to cord blood-derived mast cells. Incubation with SCF+-IL-6 for 1 week increased the IgE-dependent release as well as intracellular content of histamine in the cultured mast cells, as compared with the values obtained by incubation with SCF alone. The magnitude of these increases was higher than that for priming with SCF+IL-4. A striking difference was also found in the expression of FcεRIα between the two-factor combinations. The addition of IL-6 during FcεRI crosslinking with IgE/anti-IgE in the presence of SCF did not influence histamine secretion. When SCF, IL-6 and IL-4 were used together, a further increase was observed in the anti-IgE-dependent liberation of histamine from the cultured mast cells, compared with the two-factor combinations. These results suggest that IL-6 functions as a secretagogue for the inflammatory mediator of human mast cells in the presence of SCF. Less
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