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Basic Immunological Study of Meniere's Desease

梅尼埃病的基础免疫学研究

基本信息

批准号：
07671887
负责人：
TOMIYAMA Shunichi
金额：
$ 1.41万
依托单位：
NIPPON MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

In order to elucidate an immunological pathogenesis of Menier's disease, we investigated the mechanism of recruitment of immunocompetent cells within the inner ear, employing an animal model of the inner ear immune injury. This animal model demonstrates spontaneous nystagmus, fluctuating hearing loss with endolymphatic hydrops following antigen challenge directly to the sac of systemically presensistized guinea pigs. Immunocompetent cells could migrate into the distant region of the vestibule and cochlea, though antigen did not spread in these region. IFN-gamma was immediately generated and reached maximum at 6 hours. IFN-gamma expression was also recognized in the vestibule and the cochlea, followed by ICAM-1 expression reached maximum at 12 hours. These results suggest that inflammatory cytokine generated in the sac stimulate ICAM-1 expression in the entire inner ear and induce the migration of immnocompetent cells into the inner ear without direct antigen stimulation. Additionally, cell proliferation occurred in the sac of this animal model. Therefore, the sac may play an important role in the inner ear immune defense as well as may cause an etilogy of inner ear immune injury.Endothelin-1 (ET-1) activity was seen in the important sites of the inner ear for water balance and the transduction of the sensory nerve. ET-1 activity was strongly affected in this animal model, suggesting an important function of ET-1 for maintaing homeostasis of the microenvironment of the inner ear.Autoimmune etiology was examined in the C57BL/6 mice employing cow inner ear tissue antigen. Preliminary results showed migration of lymphocytes and PMN predominatly in the perilymphatic region, but not in the other organs. Western blot assay using cow inner ear tissue showed several positive bands reacted with serum of patients with inner ear diseases. Further investigation is essential for an autoimmune etiology of Meniere's disease.

为了阐明梅尼埃病的免疫发病机制，我们研究了内耳内免疫活性细胞的募集机制，采用内耳免疫损伤的动物模型。该动物模型显示了自发性眼球震颤、波动性听力损失和抗原直接攻击全身性致敏豚鼠的囊后的内淋巴积水。免疫活性细胞可以迁移到前庭和耳蜗的远端区域，但抗原在这些区域没有扩散。IFN-γ立即产生并在6小时达到最大值。IFN-γ在前庭和耳蜗中也有表达，随后ICAM-1的表达在12小时达到最大。这些结果表明，在囊中产生的炎性细胞因子刺激ICAM-1在整个内耳的表达，并诱导免疫活性细胞迁移到内耳没有直接的抗原刺激。此外，在该动物模型的囊中发生细胞增殖。结果表明，在内耳水平衡和感觉神经传导的重要部位存在内皮素-1（ET-1）的活性。在此动物模型中，ET-1活性受到强烈影响，提示ET-1在维持内耳微环境的稳态中具有重要功能。初步结果表明，淋巴细胞和中性粒细胞的迁移主要集中在外淋巴区，而不是在其他器官。用牛内耳组织进行免疫印迹试验，结果显示有多条阳性条带与内耳疾病患者血清反应。对梅尼埃病的自身免疫病因的进一步研究是必要的。