ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS-- ENDOTHELIAL ACTIVATION ANTIGEN

急性实验性自身免疫性脑脊髓炎--内皮激活抗原

• 批准号: 6112441
• 负责人: PAULA DORE-DUFFY
• 金额: --
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112441
• 关键词: blood brain barrier; cell cell interaction; cell migration; cell sorting; confocal scanning microscopy; cytokine; disease /disorder model; experimental allergic encephalomyelitis; inflammation; laboratory rat; lasers; leukocyte activation /transformation; mixed tissue /cell culture; multiple sclerosis; neuroimmunomodulation; northern blottings; suppressor T lymphocyte; surface antigens; vascular endothelium

Experimental autoimmune encephalomyelitis (EAE) is a T-Lymphocyte- mediated demyelinating condition and serves as an experimental model of the human disease multiple sclerosis (MS). Previous immunocytochemical studies of acute EAE in the rat have demonstrated perivascular infiltration of immune (CD4+) cells into the central nervous system (CNS). Changes in CNS endothelium as well as blood brain barrier injury occurs in both acute and chronic relapsing EAE. From studies in inflammatory disease models we know that these changes in the endothelium, loosely termed "endothelial cell activation", are often cytokine-mediated and important in leukocyte-endothelial cell interaction, and the resultant migration of leukocytes into sites of inflammation. We propose that EC activation is an important step in acute EAE induction and recovery in the Lewis rat. In specific aim #1 and #2, we will examine cytokine and leukocyte mediated EC activation in Lewis rats. Activated EC express activation antigens on the cell surface. Expression of EC activation antigens in response to cytokines and leukocyte co-culture will be measured on intact CNS microvessels and EC primary cultures using confocal laser cytometry and immunofluorescence flow cytometry. Specific aims #3 and #4 will examine EC expression of activation antigens and response to co-culture sequentially through induction and recovery from acute EAE. Emphasis will be placed on the potential role of CD4+ suppressor cells in recovery. In particular, we will study possible interactions of Ts with EC.

实验性自身免疫性脑脊髓炎（EAE）是T淋巴细胞 介导的脱髓鞘状况，并作为实验模型 人类疾病多发性硬化症（MS）。 先前的免疫细胞化学 大鼠急性EAE的研究表明周围 免疫（CD4+）细胞浸润到中枢神经系统 （CNS）。 CNS内皮以及血脑屏障损伤的变化 发生在急性和慢性复发的EAE中。 来自研究 炎症性疾病模型我们知道 内皮宽松地称为“内皮细胞激活”，通常是 细胞因子介导的白细胞 - 内皮细胞很重要 相互作用以及白细胞的结果迁移到 炎。 我们建议EC激活是重要的一步 刘易斯大鼠的急性EAE诱导和恢复。 在特定的目标＃1中 和＃2，我们将检查细胞因子和白细胞介导的EC激活 刘易斯老鼠。 活化的EC表达激活抗原在细胞上 表面。 响应细胞因子的EC激活抗原的表达 白细胞共培养将以完整的CNS微血管和 使用共聚焦激光细胞术和免疫荧光的EC原发性培养物 流式细胞仪。 具体目标＃3和＃4将检查EC的表达 激活抗原和对共培养的反应通过 急性EAE的诱导和恢复。 重点将放在 CD4+抑制细胞在恢复中的潜在作用。 特别是我们 将研究TS与EC的可能相互作用。