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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.

我们用单克隆抗体sgLFA-1、VLA-4、VLA-5、ELAM-1和ICAM-1研究了类风湿性滑膜衬里层和淋巴细胞浸润中一组粘附分子的染色模式。衬里层细胞ICAM-1和VLA-5均呈强阳性，提示ICAM-1可促进A型细胞与B型衬里层细胞的粘附，衬里层细胞可利用VLA-5锚定滑膜表面的纤维连接蛋白。在淋巴细胞丰富区和移行区，微静脉内皮细胞ELAM-1和ICAM-1均呈阳性。ICAM-1在淋巴聚集体中染色较弱，但在移行区染色较强，表明在淋巴细胞丰富区缺乏ICAM-1阳性细胞。另一方面，LFA-1染色在淋巴聚集体中非常强。这表明，存在于富含淋巴细胞的区域中的大量T4细胞被充分活化以表达实质水平的LFA-1，并且LFA-1分子也是从小静脉迁移的重要受体。为了进一步探讨类风湿关节炎滑膜血管翳形成的机制，我们进行了免疫组织化学研究。ICAM-1阳性的巨噬细胞和成纤维细胞常与淋巴样细胞接触，提示血管翳的形成过程中发生了细胞免疫反应。VLA-5分子被发现在细胞周围和interterritorial基质分布，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整联蛋白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，从而导致继发性粘附增加。