5 OXOETE AND MECHANISMS OF EOSINOPHIL ALLERGIC RESPONSES

5 OXOTE 和嗜酸性粒细胞过敏反应机制

• 批准号: 2735328
• 负责人: JOSEPH O'FLAHERTY
• 金额: $ 21.92万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-10 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2735328
• 关键词: G protein; biological signal transduction; cell line; cell migration; chemoattractants; chemotaxis; eicosanoids; eosinophil; human subject; inflammation; neutrophil; pertussis toxin; phlebotomy; protein kinase; radiotracer; receptor; receptor binding; second messengers

DESCRIPTION (Adapted from applicant's abstract and specific aims): The agents responsible for recruiting eosinophils (Eo) to sites of asthma and other diseases remain ill-defined. Chemotactic factors (CFs) are among the current suspects. However, CFs often are relatively weak Eo-stimuli, have greater potency on neutrophils (Neu), and thus seem better suited to mediate Neu-based inflammatory rather than Eo-based allergic reactions. Evidence indicates that a newly described eicosanoid, 5-oxoETE, has extreme potency, power, and selectivity in stimulating Eo migration. It resembles classical CFs in operating through presumptive receptors (Rs) that link to pertussis toxin (PT)-sensitive heterotrimeric G proteins (GPs). However, it differs from known CFs not only in strength and Eo-selectivity but also in its limited ability to stimulate non-chemotactic responses as well as its apparently complete reliance on PT-sensitive GPs. Other CFs rely on both PT-insensitive and PT-sensitive GPs. The application postulates that 5-oxoETE has a restricted range of proallergic actions on Eo; these actions proceed via dedicated Rs; these Rs link to a distinctive, identifiable subset of GPs; and these GPs regulate a correspondingly distinctive, identifiable subset of cell signals and responses. The specific aims are to: 1) Define 5-oxoETE's ability to stimulate selected responses and signals relevant to these responses in Eo and Neu; 2) Demonstrate 5-oxoETE-Rs and EPs in Eo, Neu, and differentiated HL-60 cells; and 3) Deduce the signals and functional responses regulated by specific GP classes.

描述（根据申请人的摘要和特定目的改编）： 负责招募嗜酸性粒细胞（EO）到哮喘和 其他疾病仍然不确定。 趋化因子（CFS）是 当前的嫌疑人。 但是，CF通常是相对较弱的eo-stimuli，具有 对中性粒细胞（NEU）的效力更大，因此似乎更适合介导 基于NEU的炎症而不是基于EO的过敏反应。 证据 表明一个新描述的eicosanoid，5氧化物具有极高的效力， 功率和刺激EO迁移的选择性。 它类似于古典 通过推定受体（RS）进行操作的CFS链接到百日咳 毒素（PT） - 敏感的异三聚体G蛋白（GPS）。 但是，它有所不同 来自已知的CF，不仅具有强度和EO选择性，而且还在其上 有限的刺激非化学反应及其的能力有限 显然完全依赖对PT敏感的GPS。 其他CF都依赖 对PT不敏感和PT敏感的GPS。 申请假设 5-oxoete在EO上具有限制性的促进作用；这些行动 通过专用卢比进行；这些RS链接到一个独特的，可识别的 GPS的子集；这些GP调节相应独特的， 细胞信号和响应的可识别子集。 具体目的是 至：1）定义5-oxoete刺激选定响应的能力和 与EO和NEU中的这些响应有关的信号； 2）演示 EO，NEU和分化的HL-60细胞中的5-氧气RS和EPS； 3） 推断特定GP调节的信号和功能响应 课程。