INTERLEUKIN 8 AND ACUTE PULMONARY INFLAMMATION

IL-8是炎症反应过程中产生的一种趋化因子。它有 在急性和慢性炎症性疾病中检测到 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，但一个主要的致病因素，白细胞在 炎症反应。因为IL-8将中性粒细胞吸引到 炎症，了解IL-8是如何与 它在分子水平上的两个中性粒细胞受体。明确定义 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 结合到两个受体中的每一个，这应该反映在超过 每个受体上有一个结合位点。 为了确定IL-8A和B受体上的 参与高亲和力的配体结合，突变的受体结构- 环路交换和选定的点突变-将评估 它们的配基结合亲和力和功能 转染HL60细胞。将这些研究与 正在进行的关于IL-8本身的研究应该提供关于 IL-8与其两种受体的复杂相互作用。这一分析将 阐明了受体结构/功能领域。最终 了解这些特定的配体/受体相互作用部位将 为开发抑制性的基本方法提供基础 通过开发这些区域的立体模拟来开发试剂。 与此同时，已经产生了抗兔IL-8A和B的抗体 阻断IL-8与两种受体相互作用的受体。这些遗嘱 用来评价IL-8在慢性粒细胞白血病白细胞参与中的作用 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.