| Project/Area Number |
13670445
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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 |
内科学一般
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| Research Institution | Gunma University |
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Principal Investigator |
ISHIZUKA Tamotsu Gunma University School of Medicine, Assistant, 医学部, 助手 (50302477)
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| Co-Investigator(Kenkyū-buntansha) |
OKAJIMA Fumikazu Gunma University Institute for Molecular and Cellular Regulation, Professor, 生態調節研究所, 教授 (30142748)
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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 |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Mast cell / Migration / Antigen / IgE / p38 MAP kinase / MAPKAP kinase-2 / Rho-kinase / Chemotaxis / migration / antigen / Rho-kinase / p38 MAP kinase / chemotaxis |
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| Research Abstract |
Although mast cells accumulate within the mucosal epithelial layer of patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether or not mast cells sensitized with antigen-specific IgE migrate toward the antigen. MC/9 mast cells sensitized with anti-dinitrophenyl (DNP) IgE migrated toward DNP conjugated human serum albumin (DNP-HSA). This migration was directional, and the degree was stronger than that induced by stem cell factor (SCF). IL-3 and SCF-dependent cultured mast cells derived from mouse bone marrow (IL-3/SCF-BMMC) also migrated toward the antigen. Subsequent migration mediated by the high-affinity IgE Fc receptor (FcεRI) was significantly inhibited by incubating the cells with Y-27632, a Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor, or with SB 203580, a p38 MAP kinase (p38 MAPK) inhibitor. Both p38 MAPK and MAPKAP kinase 2 were activated following FcεRI aggregation, and activation of MAPKAP kinase 2 was almost completely inhibited by 10μM SB203580. Wortmannin or a low concentration of SB203580 partially inhibited MAPKAP kinase 2, but did not block mast cell migration. On the other hand, Y-27632 did not affect the activation of MAPKAP kinase 2. These results indicate that antigen works not only as a stimulant for allergic mediators from IgE-sensitized mast cells but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of ROCK may be required for FcεRI-mediated cell migration.
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