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Experimental Pathological Analysis of Intractable Inflammatory Disease:Role of mutant genes and macrophage functions

顽固性炎症疾病的实验病理分析：突变基因和巨噬细胞功能的作用

基本信息

批准号：
61480135
负责人：
NOSE Masato
金额：
$ 3.52万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

Intractable inflammatory diseases are histopathologically characterized by granulomatous lesions associated with the accumulation of macrophages as effector cells. Owing to the immunological concepts developed in a last few years, pathogenesis of these diseases is suggested to be under the unusual host-immune response rather than the kind of pathogens. That is, the functions of macrophages and other cells belonging to mononuclear phagocyte system are regulated by unusual immune products including some lymphokines or immune complexes, and several chemical mediators released from these cells induce tissue-destruction directly or via intrinsic cell stimulation. On the other hand, these cells-play feedback actions against host immune system and modify it. Intractable inflammatory diseases may be associated with such unusual homeostatic situation.The first object in our project is to verify the propriety of this hypothesis by using several strains of immune disease mice. Thus, we have studied; 1) quantitative effect of immune complexes on the development of inflammatory lesions associated with macrophages, 2) influence of the lymphoproliferative mutant gene, lpr or gld, inducible of immunological dysfunctions upon macrophage functions, and 3) molecular characteristics of cytokines acting on macrophages, released from spleen cells in association with the lymphoproliferative gene expression or from a human T cell line.The second is to clarify the genetic factors responsible for these diseases. We have analyzed the pathologic features and macrophage functions in several strains of mice congenic of the lpr or gld gene. Moreover, it was found that particular segregated background genes contribute to the development of these diseases in association with the lymphoproliferative gene.

顽固性炎性疾病的组织病理学特征是肉芽肿病变与巨噬细胞作为效应细胞的积累相关。由于近年来免疫学概念的发展，这些疾病的发病机制被认为是由不同寻常的宿主免疫反应而不是病原体引起的。也就是说，巨噬细胞和其他属于单核吞噬细胞系统的细胞的功能受到包括一些淋巴因子或免疫复合物在内的异常免疫产物的调节，这些细胞释放的几种化学介质直接或通过细胞内在刺激诱导组织破坏。另一方面，这些细胞对宿主免疫系统发挥反馈作用并对其进行修改。难治性炎症性疾病可能与这种不寻常的体内平衡状况有关。我们项目的第一个目标是通过使用几株免疫疾病小鼠来验证这一假设的正确性。因此，我们研究了；1)免疫复合物对巨噬细胞相关炎症病变发展的定量影响；2)诱导免疫功能障碍的淋巴增生性突变基因lpr或gld对巨噬细胞功能的影响；3)与淋巴增生性基因表达相关的脾脏细胞或人T细胞系释放的巨噬细胞细胞因子的分子特征。二是阐明导致这些疾病的遗传因素。我们分析了几种携带lpr或gold基因的小鼠的病理特征和巨噬细胞功能。此外，还发现特定的分离背景基因与淋巴增生性基因有关，有助于这些疾病的发展。