HUMAN PHAGOCYTE GRANULE PROTEINS

嗜酸性粒细胞是神秘的细胞， 作为过敏性介质的有害作用的特征明确 疾病和哮喘以及仍然存在的有益特征 备受争议且知之甚少。事实上，鉴于最近的 破坏了关于嗜酸性粒细胞的假说的发现 作为体内的抗寄生虫剂，到底是什么(如果有的话)还不清楚。 嗜酸性粒细胞起到促进宿主防御的作用。考虑到这一点，我们有 开始仔细研究一些耐人寻味的关联 嗜酸性粒细胞、哮喘和过敏性支气管痉挛与疾病的联系 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 有支气管痉挛和组织损伤，因此 被一致认为是RSV疾病的恶棍，我们已经开始 考虑到嗜酸性炎症具有 “双刃剑”，与 中性粒细胞。我们实验室最近的工作清楚地表明 证明了嗜酸性粒细胞可以直接、 核糖核酸酶对呼吸道合胞病毒分离病毒粒子的破坏作用 在体外，嗜酸性粒细胞分泌蛋白之一， 嗜酸性粒细胞源性神经毒素(EDN/RNase2)可单独发挥作用 作为一种独立的抗病毒药物。本文件中描述的实验 提案将涉及嗜酸性粒细胞的生理学及其在 宿主对RSV的防御，还将考虑药理学 EDN及其相关物质的潜在作用和作用机制 核糖核酸酶作为抗病毒药物。

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.