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.

我们使用针对 LFA-1、VLA-4、VLA-5、ELAM-1 和 ICAM-1 的单克隆抗体研究了类风湿滑膜内衬层和淋巴细胞浸润中一组粘附分子的染色模式。衬层细胞呈强 ICAM-1 阳性和 VLA-5 阳性，表明 1) ICAM-1 可能有助于促进带有 ICAM-1 的 A 型细胞与 B 型衬里细胞的粘附，2) 衬层细胞细胞可以利用 VLA-5 锚定在滑膜表面的纤连蛋白上。在淋巴细胞丰富区和移行区，小静脉内皮细胞均为 ELAM-1 和 ICAM-1 阳性。 ICAM-1 染色在淋巴聚集体中较弱，但在过渡区域中较强，表明在淋巴细胞丰富的区域中缺乏 ICAM-1 携带细胞。另一方面，LFA-1 染色在淋巴聚集体中非常强。这表明存在于淋巴细胞丰富区域的大量T4细胞被充分激活以表达高水平的LFA-1，并且LFA-1分子是从小静脉移出的重要受体。此外，为了研究类风湿关节炎中滑膜血管翳形成的机制，进行了免疫组织化学研究。 ICAM-1阳性巨噬细胞和成纤维细胞经常被发现与淋巴细胞接触，表明血管翳形成过程中发生了细胞免疫反应。 VLA-5 分子分布在细胞周和域间基质中，强烈表明 VLA-5 和软骨基质之间的受体-配体相互作用可能发生在血管翳形成的早期阶段。此外，b1整合素的增加可能是血管翳生长所必需的，也是VLA分子上调所必需的，进而导致附着力增加。