Chemokines and chemokine receptors in multiple sclerosis

多发性硬化症中的趋化因子和趋化因子受体

• 批准号: 6565279
• 负责人: Richard M. Ransohoff
• 金额: $ 21.35万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6565279
• 关键词: T lymphocyte; animal tissue; chemokine; cytokine receptors; experimental allergic encephalomyelitis; human tissue; inflammation; macrophage; multiple sclerosis

DESCRIPTION (adapted from page 125). The project will study chemokine receptors on T cells and mononuclear phagocytes (blood-borne monocytes, macrophages, microglia) in a set of related tissues: Blood and CSF from MS patients, and blood and brains from marmosets with autoimmune disease. The stated hypothesis is that "chemokine receptors are significantly involved in leukocyte invasion, differentiation and activation in the CNS during MS." "Functional significance" will be studied by "quantitating receptor-bearing cells." It is expected that the work will "define molecular targets for therapy." (pg. 125, first par.) Aim 1 defines chemokine receptors on T cells in MS brain. The hypothesis is that T cells in MS lesions representing different stages of disease activity or patterns of demyelination will show different chemokine receptor profiles. The receptors to be studied are CXCR3 and CCR5, characteristic of Th1 cells; CCR4 and CCR3, characteristic of Th2 cells; and CXCR4, expressed by naive T cells. The PI will also ask which cells express IP-10 and RANTES, which are ligands for the Th1 receptors. Aim 2 performs a similar analysis for mononuclear phagocytes in MS brain, to test a similar hypothesis. The receptors to be studied are CCR2, characteristic of monocytes; CCR1, characteristic of macrophages; and CCR5, characteristic of phagocytic macrophages and activated microglia. Aim 3 defines the same receptors on cells from blood and CSF of MS patients (3a), and blood and brain from marmosets (3b). It is explained that AIM 3 "examines the functional significance of receptor expression (p. 125, last 3 lines)."

说明(改编自第125页)。该项目将研究趋化因子受体。 T细胞和单核巨噬细胞(血源性单核细胞、巨噬细胞、 小胶质细胞)在一组相关组织中：MS患者的血液和脑脊液，以及 患有自身免疫性疾病的绒猴的血液和大脑。所陈述的假设 是“趋化因子受体在白细胞侵袭中起重要作用， 多发性硬化时中枢神经系统的分化与激活“功能意义” 将通过“量化受体承载细胞”进行研究。预计 这项工作将“确定治疗的分子靶点”。(PG.125杆，第一标准杆。) 目的1定义MS脑内T细胞上的趋化因子受体。假设是 多发性硬化症皮损中代表疾病活动不同阶段的T细胞 脱髓鞘的模式将显示不同的趋化因子受体特征。 拟研究的受体为Th1细胞特有的CXCR3和CCR5； CCR4和CCR3，Th2细胞的特征；以及CXCR4，由幼稚T细胞表达 细胞。PI还将询问哪些细胞表达IP-10和RANTES，哪些是 Th1受体的配体。 AIM 2对MS脑中的单核吞噬细胞进行了类似的分析，以 测试一个类似的假设。待研究的受体为CCR2，特性 单核细胞；CCR1，巨噬细胞的特征；以及CCR5，巨噬细胞的特征 吞噬巨噬细胞和激活的小胶质细胞。 目的3定义MS患者血液和脑脊液细胞上相同的受体 (3a)和来自绒猴的血液和脑(3b)。据解释，AIM 3 研究了受体表达的功能意义(第125页，最后3页 行)。“