5 OXOETE AND MECHANISMS OF EOSINOPHIL ALLERGIC RESPONSES

描述(根据申请者的抽象和具体目标改编)： 负责将嗜酸性粒细胞(EO)招募到哮喘和哮喘部位的代理 其他疾病的定义仍然不明确。趋化因子(CFs)是 目前的嫌疑犯。然而，CFS往往是相对较弱的EO刺激，具有 对中性粒细胞(Neu)的更大效力，因此似乎更适合于调解 以神经为基础的炎性反应，而不是以EO为基础的过敏反应。证据 表明一种新描述的二十烷类化合物5-oxoETE具有极强的效力， 在刺激EO迁移方面的能力和选择性。它看起来像古典音乐 CFS通过与百日咳相关的推定受体(Rs)发挥作用 毒素(PT)敏感的异三聚体G蛋白(GP)。然而，它是不同的 从已知的CFS不仅在强度和EO选择性方面，而且在其 刺激非趋化反应的能力有限以及其 显然完全依赖对PT敏感的全科医生。其他CFS同时依赖于这两个 PT不敏感和PT敏感的GP。申请的前提是 5-oxoETE对EO的促过敏作用范围有限；这些作用 通过专用R进行；这些R链接到独特的、可识别的 GP的子集；并且这些GP调节相应的独特的、 小区信号和响应的可识别子集。具体目标是 为了：1)确定5-oxoETE刺激选定反应和 与EO和Neu中的这些反应相关的信号；2)证明 EO、Neu和分化的HL-60细胞中的5-oxoETE-Rs和EPs； 推断受特定GP调控的信号和功能反应 上课。

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.