HUMAN LYMPHOCYTE CHEMOATTRACTANTS

人类淋巴细胞趋化剂

• 批准号: 3083187
• 负责人: STEPHEN JOEL ROTH
• 金额: $ 8.37万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3083187
• 关键词: SDS polyacrylamide gel electrophoresis; T lymphocyte; antibody formation; binding proteins; cell adhesion; cell migration; chemoattractants; chemotaxis; complementary DNA; flow cytometry; high performance liquid chromatography; human tissue; immunoaffinity chromatography; inflammation; laboratory mouse; leukocyte activation /transformation; lymphocyte; messenger RNA; molecular cloning; monoclonal antibody; nucleic acid sequence; protein purification; protein structure function; urinalysis

Leukocyte migration through vascular endothelium at sites of injury is the central event in the inflammatory response. Soluble mediators known as chemoattractants activate leukocytes and direct their migration through the vessel wall. While several of the chemoattractants which recruit neutrophils and monocytes have been identified and characterized, little is known about lymphocyte chemoattractants. Based on the behavior of specific lymphocyte subsets in immune surveillance and inflammation, we hypothesize that at least two different lymphocyte chemoattractants exist. The goals of our proposed research are to identify and purify human lymphocyte chemoattractants, to characterize their structure and function, and to study the mechanisms by which they activate lymphocyte binding and migration. Our strategy for identifying these molecules involves screening likely sources using lymphocyte chemotaxis assays and binding assays which detect changes in the binding of integrin adhesion molecules on the lymphocyte surface. We expect to identify multiple small proteins; our strategy for characterization will begin with purification and progress to functional studies, monoclonal antibody production, and complementary DNA isolation and sequence analysis. The identification and characterization of these molecules should help define the molecular mechanisms of lymphocyte migration, and provide new targets for the therapy of chronic inflammatory diseases.

白细胞通过受伤部位的血管内皮迁移是 炎症反应中的中央事件。 可溶性介体称为 化学吸引剂激活白细胞，并指导其迁移 船墙。 而几种招募的趋化剂 中性粒细胞和单核细胞已被鉴定出来，并且表征很少 有关淋巴细胞趋化剂的已知。 基于特定的行为 免疫监测和炎症中的淋巴细胞亚群，我们假设 至少存在两个不同的淋巴细胞化学吸引剂。 目标 我们提出的研究是识别和净化人类淋巴细胞 化学吸引剂，以表征其结构和功能，并 研究它们激活淋巴细胞结合的机制和 迁移。 我们识别这些分子的策略涉及筛查 可能使用淋巴细胞趋化测定和结合测定的来源 检测整联蛋白粘附分子在结合上的变化 淋巴细胞表面。 我们期望鉴定多种小蛋白质；我们的 表征策略将从净化开始，并进步 功能研究，单克隆抗体的产生和互补DNA 隔离和序列分析。 标识和表征 这些分子应有助于定义分子机制 淋巴细胞迁移，并为治疗慢性提供了新的靶标 炎症性疾病。