Research on migration of sensitized mast ceils toward the antigen

致敏肥大细胞向抗原迁移的研究

• 批准号: 13670445
• 负责人: ISHIZUKA Tamotsu
• 金额: $ 0.96万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670445/
• 关键词: Mast cell; Migration; Antigen; IgE; p38 MAP kinase; MAPKAP kinase-2; Rho-kinase; Chemotaxis; migration; antigen; Rho-kinase; p38 MAP kinase; chemotaxis

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.

尽管肥大细胞积聚在过敏性鼻炎和支气管哮喘患者的粘膜上皮层中，但负责的趋化因子却不确定。我们研究了用抗原特异性IgE敏感的肥大细胞是否迁移到抗原。 MC/9肥大细胞对抗二硝基苯基（DNP）IgE敏感，迁移到DNP共轭人血清专辑（DNP-HSA）。该迁移是定向的，程度比干细胞因子（SCF）诱导的迁移更强。源自小鼠骨髓（IL-3/SCF-BMMC）的IL-3和依赖于SCF的培养肥大细胞也迁移到抗原。通过将细胞与Y-27632（一种与RHO相关的盘绕螺旋形成蛋白激酶（ROCK）抑制剂）一起孵育，通过高亲和力IgE FC受体（FCεRI）介导的随后的迁移被显着抑制。在FcεRI聚集后激活P38 MAPK和MAPKAP激酶2，MAPKAP激酶2的激活几乎被10μMSB203580完全抑制。 Wortmannin或低浓度的SB203580部分抑制了MAPKAP激酶2，但没有阻断肥大细胞迁移。另一方面，Y-27632不影响MAPKAP激酶2的激活。这些结果表明，抗原不仅可以作为来自IgE敏感肥大细胞的过敏介质的刺激性，而且还可以作为肥大细胞的趋化因子。 FcεRI介导的细胞迁移可能需要P38 MAPK激活和岩石的Rho依赖性激活。