THE ROLE OF B7 INTEGRIN AND ADHESION OF T LYMPHOCYTES

B7 整合素的作用和 T 淋巴细胞的粘附

• 批准号: 2445015
• 负责人: MARK A TIDSWELL
• 金额: $ 8.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-03-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445015
• 关键词: T cell receptor; T lymphocyte; antibody; biological signal transduction; cell adhesion; complementary DNA; cytoplasm; enzyme activity; flow cytometry; genetic mapping; human subject; integrins; interleukin 1; leukocyte adhesion molecules; mucosal immunity; phorbols; phosphoproteins; protein kinase C; protein sequence; protein structure function; tissue /cell culture; transfection; transforming growth factors; vascular endothelium; western blottings

The long-term objective is to determine the role of leukocytes in human lung disease. The proposed studies may lead to therapies to modify the immune response. The proposed work will be an investigation of an adhesion molecule that is found on human lymphocytes and eosinophils. This adhesion molecule, integrin alpha4beta7, is one of the integrin family of cell surface proteins. Integrins mediate adhesion of cells to extracellular matrix proteins and to vascular endothelial cells. Integrins are necessary for leukocyte migration into tissues. Integrin alpha4beta7 was identified in human lung airway leukocytes. Integrin alpha4beta7 mediates cell adhesion to mucosal addressin, a protein located on endothelium in mucosal lymphoid tissue. Leukocytes that adhere to mucosal addressin then migrate into these tissues. Thus, alpha4beta7 and mucosal addressin interact and direct leukocytes into specific tissues. The aims of this work are to determine the amino acid residues of the cytoplasmic domain of the beta7 integrin subunit that are involved in signal transduction by alpha4beta7, and regulation of cell adhesion mediated by alpha4beta7. The beta7 subunit cDNA will be mutated to alter the structure and amino acid sequence of the cytoplasmic domain. The mutated beta7 proteins will be expressed in cultured cell lines. In vitro adhesion assays will demonstrate the effects of the mutations on cell adhesion and on signal transduction by alpha4beta7. Experiments will then analyze the function of alpha4beta7 in human T cells. The results of these experiments could suggest therapies for immune and inflammatory diseases of the lung.

长期目标是确定白细胞在人类中的作用 肺部病。 拟议的研究可能导致疗法修改 免疫反应。 拟议的工作将是对 在人淋巴细胞和嗜酸性粒细胞上发现的粘附分子。 这种粘附分子，整合蛋白alpha4beta7是整合素之一 细胞表面蛋白家族。 整联蛋白介导细胞的粘附于 细胞外基质蛋白和血管内皮细胞。 整联蛋白对于白细胞迁移到组织中是必需的。 整合素 在人肺气道白细胞中鉴定出α4Beta7。 整合素 alpha4beta7介导细胞粘附到粘膜地址，这是一种蛋白质 在粘膜淋巴组织中的内皮上。 遵守的白细胞 然后，粘膜地址迁移到这些组织中。 因此，alpha4beta7和 粘膜地址与特定组织相互作用并将白细胞引导到特定的组织中。 这项工作的目的是确定 与参与的β7整合素亚基的细胞质结构域 α4Beta7的信号转导和细胞粘附的调节 由alpha4beta7介导。 beta7亚基cDNA将被突变以改变 细胞质结构域的结构和氨基酸序列。 这 突变的β7蛋白将在培养的细胞系中表达。 体外 粘附测定将证明突变对细胞的影响 粘附和信号转导的α4Beta77。 然后将进行实验 分析人类T细胞中α4Beta7的功能。 结果 这些实验可以提示免疫和炎症的疗法 肺部疾病。