INTERLEUKIN 8 AND ACUTE PULMONARY INFLAMMATION

IL-8是在炎症反应期间产生的趋化因子。 它有 在急性和慢性炎性疾病中检测到， 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不仅是 目前，但主要的病原体白细胞浸润过程中 炎症反应。 因为IL-8吸引PMNs进入一个区域， 因此，了解IL-8如何与炎症相互作用变得非常重要。 它的两个亲脂性受体在分子水平上。 明确定义 受体和配体的结构， IL-8的结合是必需的。 IL-8上不止一个区域似乎 结合到两个受体中的每一个，这应该反映在超过 每个受体上都有一个结合位点 为了确定IL-8 A和B受体上的位点 参与高亲和力配体结合，突变的受体结构- 环交换和选择的点突变-将评估 它们的配体结合亲和力和它们的功能能力 转染HL 60细胞。 这些研究与 目前正在进行的IL-8研究本身应提供明确的定义， IL-8与其两种受体的复杂相互作用。 该分析将 阐明受体结构/功能领域。 最终 配体/受体相互作用的这些特定位点的知识将 为合理方法提供基础， 通过开发这些区域的空间模拟物来制备试剂。 同时，已经产生了针对兔IL-8 A和B的抗体 受体阻断IL-8与两种受体的相互作用。 这些将 用于评估IL-8在白细胞参与免疫反应中的作用 家兔肺部炎症模型。

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.