REGULATION OF LEUKOCYTE AND VESSEL WALL CELL ADHESION

白细胞和血管壁细胞粘附的调节

• 批准号: 6202176
• 负责人: JOHN Marshall HARLAN
• 金额: $ 25.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6202176
• 关键词: B lymphocyte; Primates; atherosclerosis; cell cell interaction; cell migration; cellular pathology; confocal scanning microscopy; cytoskeleton; enzyme linked immunosorbent assay; human tissue; inflammation; integrins; laboratory mouse; laboratory rabbit; leukocyte adhesion molecules; macrophage; monoclonal antibody; monocyte; phosphoproteins; receptor; selectins; thiols; vascular endothelium; western blottings

Mononuclear leukocyte adherence to endothelium is a pivotal event in the inflammatory phase of arterial diseases such as atherosclerosis. The current model of leukocyte emigration predicts that leukocytes first adhere transiently via selectin receptors with subsequent firm adherence mediated by integrin receptors, triggered to a high avidity state by local stimuli. This proposal will examine the regulation of leukocyte adhesion, focusing on the role of selectin receptors in monocyte emigration in the arterial circulation and the regulation of beta1 integrin affinity. The following Specific Aims are proposed: 1) to determine the role of selectins in mononuclear phagocyte emigration into the arterial wall of rabbits following stimulation with chemotactic agents; 2) to determine the effect of affinity modulation by the activating beta1 MAb 8A2 in vivo; 3) to determine the adhesion pathway involved in beta1 MAb 4B5-stimulated leukocyte adherence to endothelium; 4) to examine mechanisms of high affinity mononuclear leukocyte adhesion; and 5) to determine the cytoskeletal associations of high affinity beta1 receptors.

单核白细胞粘附于内皮细胞是单核细胞增生的关键事件。 动脉疾病如动脉粥样硬化的炎症阶段。 的 目前的白细胞迁移模型预测， 通过选择素受体短暂粘附，随后牢固粘附 由整联蛋白受体介导，由局部免疫反应触发至高亲合力状态， 刺激。 本提案将研究白细胞粘附的调节， 重点是选择素受体在单核细胞迁移中的作用， 动脉循环和β 1整合素亲和力的调节。 的 提出了以下具体目标：1）确定 单核巨噬细胞迁移到动脉壁的选择素 用趋化剂刺激后的兔; 2）确定 体内活化β 1 MAb 8A 2的亲和力调节作用; 3） 为了确定β 1 MAb 4 B5刺激的 白细胞粘附于内皮细胞; 4）检查高内皮细胞粘附的机制， 单核白细胞粘附的亲和力;和5）确定 高亲和力β 1受体的细胞骨架结合。