Role of macrophages in bone destruction in cholesteatoma otitis media

巨噬细胞在胆脂瘤中耳炎骨质破坏中的作用

基本信息

批准号：
13671811
负责人：
SAKAGAMI Masafumi
金额：
$ 2.24万
依托单位：
Hyogo College of Medicine
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-13671811/
关键词：
macrophage osteoclast cholesteatoma otitis media catepsin K TRAP osteopontin cytokine tympanoplasty

项目摘要

Many studies reported that the typical osteoclasts are infrequent in human chlesteatoma biopsies. We previously reported that many macrophages were found in subepithelial tissue under cholesteatoma matrix. Therefore, we hypothesized that the macrophage has an activity of the osteoclast-like cell. Under informed consent to the patients, cholesteatoma matrix, subepithelial granulation tissue and ossicles adjacent to matrix were taken out for specimens during tympanoplasty.Results were the followings ; 1) many multinuclear cells were stained in subepithelial connective tissue with immunohistochemistry of CD68 antibody. 2) Cathepsin K and TRAP (tartrate-resistant acid phosphatase), which are usually expressed in osteoclasts, were observed in macrophages with immunohistochemistry and in situ hybridization. 3) Cathepsin K and TRAP were also recognized by RT-PCR. 4) OPN (osteopontin), which is necessary to attach to the surface of osteoclasts, was observed in macrophages with immunohistochemistry and in situ hybridization. 5) Cytokines of cholesteatoma matrix and granulation tissue (IL-1, IL-6, TNF-a, M-SCP) were expressed in the culture liquid.These findings suggested that inflammatory cytokines induced macrophages from the bone marrow to subepithelial connective tissue and that they became osteoclast-like macrophages to attach to the bone surface.

许多研究报告称，典型的破骨细胞在人类胆脂瘤活检中并不常见。我们之前报道过，在胆脂瘤基质下的上皮下组织中发现了许多巨噬细胞。因此，我们推测巨噬细胞具有破骨细胞样细胞的活性。经患者知情同意，鼓室成形术时取出胆脂瘤基质、上皮下肉芽组织及邻近基质的小骨作为标本。结果如下： 1)CD68抗体免疫组化显示上皮下结缔组织中有大量多核细胞染色。 2)通过免疫组化和原位杂交在巨噬细胞中观察到通常在破骨细胞中表达的组织蛋白酶K和TRAP(抗酒石酸酸性磷酸酶)。 3)组织蛋白酶K和TRAP也被RT-PCR识别。 4)通过免疫组织化学和原位杂交在巨噬细胞中观察到附着在破骨细胞表面所必需的OPN（骨桥蛋白）。 5）培养液中胆脂瘤基质和肉芽组织的细胞因子（IL-1、IL-6、TNF-a、M-SCP）均有表达。这些结果表明，炎症细胞因子诱导巨噬细胞从骨髓向上皮下结缔组织转移，它们变成破骨细胞样巨噬细胞附着在骨表面。