CELL ADHESION MOLECULES IN OCULAR INFLAMMATION

细胞粘附分子是细胞表面的重要蛋白质， 致敏和白细胞向炎症部位的迁移。 我们正在研究细胞粘附分子在眼内的表达， 炎症，研究细胞粘附分子的阻断， 治疗葡萄膜炎和其它眼部炎性疾病，和 检测免疫抑制剂对细胞粘附的影响 实验性自身免疫性葡萄膜炎（EAU）眼内的分子表达。 我们以前的研究表明，细胞间粘附分子1（ICAM-1）是一种细胞间粘附分子。 EAU患者眼内炎性细胞浸润前表达。 进一步的实验表明，抗ICAM-1和ICAM-1 mRNA的单克隆抗体可用于治疗糖尿病。 其反受体淋巴细胞功能相关抗原1（LFA-1） 抑制小鼠EAU发展。 我们证明了细胞粘附分子对这两种细胞都很重要， 抗原致敏和炎性细胞浸润到眼中， 附加的几组实验表明：（1） 抗ICAM-1和LFA-1的单克隆抗体将阻止 内毒素诱导的眼炎性细胞浸润，和 重要是，这些抗体甚至可以抑制眼部炎症， 当注意到炎症迹象后给药时;和（2） ICAM-1和LFA-1单克隆抗体在体外可抑制ICAM-1和LFA-1的表达， 增殖的葡萄膜细胞系的干扰， 淋巴细胞和抗原呈递细胞之间的相互作用。 这些 结果表明，细胞粘附分子在 葡萄膜炎发展和细胞粘附分子的阻断 为炎症性眼病的治疗提供了新的途径 疾病 最后，我们检查了免疫抑制剂对 EAU动物中细胞粘附分子的表达。 眼部 细胞粘附分子的表达延迟并下调， 用皮质类固醇和环孢霉素治疗的动物， 用视网膜S抗原免疫。 细胞粘附下调 分子表达可能是一种机制， 免疫抑制剂抑制眼部炎症。

Cell adhesion molecules are surface proteins important for antigen sensitization and the migration of leukocytes to sites of inflammation. We are studying the expression of cell adhesion molecules in ocular inflammation, investigating the blocking of cell adhesion molecules as a treatment for uveitis and other ocular inflammatory diseases, and examining the effect of immunosuppressive agents on cell adhesion molecule expression in eyes with experimental autoimmune uveitis (EAU). We previously showed that intercellular adhesion molecule 1 (ICAM-1) is expressed in eyes with EAU before the infiltration of inflammatory cells. Further experiments showed that monoclonal antibodies against ICAM-1 and its counter-receptor lymphocyte function-associated antigen 1 (LFA-1) inhibit EAU development in mice. We demonstrated that cell adhesion molecules are important for both antigen sensitization and inflammatory cell infiltration into the eye, with additional sets of experiments showing the following: (1) that monoclonal antibodies against both ICAM-1 and LFA-1 will prevent inflammatory cell infiltration of the eye induced by endotoxin, and importantly that these antibodies can inhibit ocular inflammatory even when administered after signs of inflammation have been noted; and (2) that monoclonal antibodies against ICAM-1 and LFA-1 can inhibit in vitro proliferation of a uveitogenic cell line by interfering with the interaction between lymphocytes and antigen-presenting cells. These results suggest that cell adhesion molecules play an important role in the development of uveitis and that blockage of cell adhesion molecules may provide a new therapeutic approach for patients with inflammatory eye disease. Finally we examined the effect of immunosuppressive agents on the expression of cell adhesion molecules in animals with EAU. Ocular expression of cell adhesion molecules was delayed and downregulated in animals treated with corticosteroids and cyclosporine following immunization with retinal S-antigen. Downregulation of cell adhesion molecule expression may be one of the mechanisms by which immunosuppressive agents inhibit ocular inflammation.