THE ROLE OF ADHESION MOLECULES IN THE CHRONICITY AND JOINT DESTRUCTION OF ARTHRITEDES

粘附分子在关节炎慢性和关节破坏中的作用

基本信息

批准号：
07457336
负责人：
ISHIKAWA Hitoshi
金额：
$ 4.54万
依托单位：
KOBE UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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

We studied the staining pattern of a group of adhesion molecules in the lining layr and lymphocytic infiltrates of the rheumatoid synovial membrane, using monoclonal antibodies sgainst LFA-1, VLA-4, VLA-5, ELAM-1 and ICAM-1. The cells of the lining layr were strongly ICAM-1 positive and VLA-5 positive, suggesting 1) that ICAM-1 may function to facilitate the adhesion of ICAM-1 bearing type A cells to type B lining cells and 2) that the lining cells may utilize VLA-5 for anchorage to fibronectin at surface of the synovial membrane. In the lymphocyte-rich and transitional areas, the endothelial cells of the venules were both ELAM-1 and ICAM-1 positive. ICAM-1 staining was weak in lymphoid aggregate, but strong in the transitional areas, indcating a paucity of ICAM-1 bearing cells in the lymphocyte-rich areas. On the other hand, LFA-1 staining was very strong in the lymphoid aggregates. This suggested that the large numbers of T4 cells present in the lymphocyte-rich areas are sufficiently activated to express substatial levels of LFA-1, and also that the LFA-1 molecules is an important receptor for emigration from venules. Furthermore to investigate the mechanism of synovial pannus formation in rheumatoid arthritis, immunohistochemical studies were carried out. ICAM-1 positive macrophages and fibroblasts were often found to be contact with lymphoid cells, suggesting that a cellular immune reaction occurs in the formation of the pannus. The VLA-5 molecules was found in a pericellular and interterritorial matrix distribution, strongly suggesting that a receptor-ligand interaction between VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in b1 integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to indrease attachment.

我们使用单克隆抗体Sgainst LFA-1，VLA-4，VLA-4，VLA-5，VLA-5，ELAM-1和ICAM-1研究了类风湿滑膜膜的一组粘附分子的染色模式和类风湿膜的淋巴细胞浸润。 Layr衬里的细胞具有强烈的ICAM-1阳性和VLA-5阳性，这表明ICAM-1可以起作用，以促进ICAM-1轴承A型细胞对B型衬里细胞的粘附，以及2）衬里细胞可利用VLA-5用于锚固，以锚固至原膜膜表面的纤维蛋白。在淋巴细胞富含淋巴细胞和过渡区域，静脉内皮细胞均为ELAM-1和ICAM-1阳性。 ICAM-1染色在淋巴骨料中较弱，但在过渡区域中很强，促成富含淋巴细胞的区域中ICAM-1轴承细胞的缺乏。另一方面，LFA-1染色在淋巴骨料中非常强。这表明，淋巴细胞中存在的大量T4细胞被充分激活以表达LFA-1的替代水平，并且LFA-1分子是从静脉移民的重要受体。此外，要研究类风湿关节炎中滑膜pandus形成的机理，进行了免疫组织化学研究。经常发现ICAM-1阳性巨噬细胞和成纤维细胞与淋巴样细胞接触，这表明在Pannus的形成中发生了细胞免疫反应。 VLA-5分子是在细胞周围和地际基质分布中发现的，强烈表明VLA-5与软骨基质之间的受体配体相互作用可能在Pannus组的早期阶段发生。此外，B1整联蛋白的增加可能是pannus的生长以及VLA分子的上调所必需的，其次导致附着。