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The mechanism and the regulation of nerve-mast cell interactions in skin allergic diseases.

皮肤过敏性疾病中神经-肥大细胞相互作用的机制及调控。

基本信息

批准号：
11670832
负责人：
HIDE Michihiro
金额：
$ 2.24万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

To know the role of the nerve system in allergic skin diseases, we investigated the release of histamine, LTB4 and TNFα from skin mast cells in response to substance P, and the mechanism of mast cell-growth and differentiation. Every skin tissues obtained from all human donors by surgical operations released histamine, but tissues of only 34.8% and 80% of the donors released LTB4 and TNFα, respectively in response to substance P. The release of TNFα, but not that of histamine was inhibited either by preincubation of the tissues with steroid or MAP kinase (ERK) inhibitor. We report a case of urticaria, who developed eruptions together with the abnormal brain waves on exercise, perspiration or psychological tensjon, suggesting that abnormal activities of central nerve system could associate with skin allergic reactionsWe next studied about the functional heterogeneity, differentiation and growth of skin mast cells, using co-culture system of mouse bone marrow-derived mast cells and NIH-3T3 fibroblasts. When the mast cells were cultured with SCF alone, they released LTB4, but not histamine in response to substance P. On the other hand, when mast cells lacking signaling machinery for c-kit, the receptor for SCF, were cultured with fibroblasts, they released histamine, but not LTB4 in response to substance P. The release of LTB4 from mouse mast cells was inhibited by either steroid, a MAP kinase-inhibitor or an anti-allergic H1-blocker. The release of LTB4 was not correlated to the increase of intracellular Ca^<2+> concentration. These results indicate that the growth and differentiation of skin mast cells were induced by both SCF and non-SCF fibroblast-derived factor.

为了解神经系统在变态反应性皮肤病中的作用，我们研究了P物质刺激皮肤肥大细胞释放组胺、LTB_4和TNFα的情况，以及肥大细胞生长和分化的机制。所有供者的皮肤组织均可释放组胺，但只有34.8%的供者皮肤组织释放LTB_4，80%的供者皮肤组织释放TNF α。本文报告一例荨麻疹患者，在运动、出汗或心理紧张时出现皮疹并伴有异常脑电波，提示中枢神经系统活动异常可能与皮肤过敏反应有关。当肥大细胞单独与SCF一起培养时，它们释放LTB 4，但不响应P物质而释放组胺。另一方面，当肥大细胞缺乏c-kit（SCF受体）的信号传导机制时，它们与成纤维细胞一起培养时，它们释放组胺，但不响应P物质而释放LTB 4。MAP激酶抑制剂或抗过敏性H1阻断剂。LTB 4的释放与细胞内Ca^<2+>浓度的升高无关。这些结果表明，皮肤肥大细胞的生长和分化的SCF和非SCF的成纤维细胞衍生因子的诱导。