INTERLEUKIN 8 AND ACUTE PULMONARY INFLAMMATION

白细胞介素 8 与急性肺部炎症

• 批准号: 6074387
• 负责人: INGRID U SCHRAUFSTATTER
• 金额: $ 9.99万
• 依托单位: LA JOLLA INST FOR MOLECULAR MEDICINE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6074387
• 关键词: adult respiratory distress syndrome; cytokine receptors; disease /disorder model; gene mutation; immunologic assay /test; inflammation; interleukin 8; laboratory rabbit; lung injury; point mutation; protein structure function; receptor binding; transfection

IL-8 is a chemokine produced during the inflammatory response. It has been detected in acute and chronic inflammatory diseases including acute respiratory distress syndrome, cystic fibrosis, chronic bronchitis and rheumatoid arthritis. The evidence is increasing that IL-8 is not only present, but a major causative agent for leukocyte infiltration during the inflammatory response. Because IL-8 attracts PMNs into an area of inflammation, it becomes important to understand how IL-8 interacts with its two neutrophilic receptors on the molecular level. Clear definition of the receptor and ligand structures that account for high affinity binding of IL-8 is necessary. More than one region on IL-8 appears to bind to each of the two receptors which should be reflected in more than one binding site on each receptor. In order to define the sites on the IL-8 A and B receptors that are involved in high affinity ligand binding, mutated receptor constructs - both loop exchange and selected point mutations - will be assessed for their ligand binding affinity and their functional capacity following transfection into HL60 cells. The combination of these studies with ongoing studies on IL-8 itself should provide clear definition of the complex interaction of IL-8 with its two receptors. This analysis will shed light on the field of receptor structure/function. Eventually knowledge of these specific sites of ligand/receptor interaction will provide a foundation for rationale approaches to develop inhibitory reagents by developing steric mimics of these regions. In the meantime antibodies have been produced to rabbit IL-8 A and B receptors that block IL-8 interaction with both receptors. These will be used to evaluate the role of IL-8 in leukocyte participation in a rabbit model of pulmonary inflammation.

IL-8 是炎症反应过程中产生的趋化因子。 它有 在急性和慢性炎症性疾病中检测到，包括急性 呼吸窘迫综合征、囊性纤维化、慢性支气管炎和 类风湿关节炎。 越来越多的证据表明 IL-8 不仅 存在，但是白细胞浸润的主要致病因素 炎症反应。 因为 IL-8 会吸引 PMN 进入某个区域 炎症，了解 IL-8 如何与炎症相互作用变得很重要 它在分子水平上有两个中性粒细胞受体。 明确的定义 造成高亲和力的受体和配体结构 IL-8 的结合是必要的。 IL-8 上的多个区域似乎 与两个受体中的每一个结合，这应该反映在超过 每个受体上有一个结合位点。 为了定义 IL-8 A 和 B 受体上的位点， 参与高亲和力配体结合、突变受体构建 - 环交换和选定的点突变 - 将进行评估 它们的配体结合亲和力和功能能力如下 转染HL60细胞。 这些研究的结合 正在进行的关于 IL-8 本身的研究应提供明确的定义 IL-8 与其两个受体的复杂相互作用。 本次分析将 阐明受体结构/功能领域。 最终 了解配体/受体相互作用的这些特定位点将 为开发抑制性方法提供基础 通过开发这些区域的空间模拟物来制备试剂。 同时已生产出针对兔 IL-8 A 和 B 的抗体 阻断 IL-8 与两种受体相互作用的受体。 这些将 用于评估 IL-8 在白细胞参与 兔肺部炎症模型。