HUMAN PHAGOCYTE GRANULE PROTEINS

嗜酸性粒细胞是一种神秘的细胞， 作为过敏性疾病的介质， 疾病和哮喘以及仍然存在的有益特征， 有争议的和不太了解的。事实上，鉴于最近 这些发现破坏了关于嗜酸性粒细胞的假设， 作为体内抗寄生虫剂，根本不清楚是什么（如果有的话） 嗜酸性粒细胞能促进宿主防御。考虑到这一点，我们 开始仔细研究一些有趣的关联， 连接嗜酸性粒细胞、哮喘和过敏性支气管痉挛， 由呼吸道病毒引起，最明显的是由 呼吸道合胞病毒（RSV）。虽然嗜酸性粒细胞与 支气管痉挛和组织损伤， 被一致认为是RSV疾病的罪魁祸首，我们已经开始 考虑嗜酸性粒细胞性炎症有可能 “双刃剑”，类似于更仔细地研究， 中性粒细胞我们实验室最近的工作显然 表明嗜酸性粒细胞可以介导直接的， 核糖核酸酶依赖的RSV分离病毒体的破坏 体外，嗜酸性粒细胞分泌蛋白之一， 嗜酸性粒细胞衍生的神经毒素（EDN/ RNase 2），可单独发挥作用 作为一种独立的抗病毒药物。本文中描述的实验 提案将讨论嗜酸性粒细胞的生理学及其在 宿主对RSV的防御，也将考虑药理学 EDN的潜力和作用机制及相关 核糖核酸酶作为抗病毒剂。

Eosinophils are enigmatic cells with well-characterized detrimental roles as mediators of allergic diseases and asthma and beneficial features that remain controversial and poorly understood. Indeed, in light of the recent findings that have undermined the hypotheses regarding eosinophils as antiparasitic agents in vivo, it is not at all clear what (if anything) eosinophils do to promote host defense. With this in mind, we have begun to look carefully at some of the intriguing associations that link eosinophils, asthma and allergic bronchospasm, and diseases caused by respiratory viruses, most notably that caused by respiratory syncytial virus (RSV). While eosinophils are associated with bronchospasm and tissue damage, and thus have been uniformly perceived as the villains of RSV disease, we have begun to consider the possibility that eosinophilic inflammation has a "double-edged sword," similar to that studied more carefully in neutrophils. Recent work in our laboratory has clearly demonstrated that eosinophils can mediate the direct, ribonuclease-dependent destruction of isolated virions of RSV in vitro, and that one of the eosinophil secretory proteins, the eosinophil-derived neurotoxin (EDN/ RNase 2), can function alone as an independent antiviral agent. The experiments described in this proposal will address the physiology of eosinophils and their role in host defense against RSV and will also consider the pharmacologic potential and mechanism of action of EDN and related ribonucleases as antiviral agents.