HUMAN PHAGOCYTE GRANULE PROTEINS

嗜酸性粒细胞是一种神秘的细胞，其作为过敏性疾病和哮喘的介质具有明确的有害作用，但其有益特征仍存在争议且知之甚少。事实上，根据最近的研究结果，已经破坏了关于嗜酸性粒细胞在体内作为抗寄生虫剂的假设，它是不是在所有清楚什么（如果有的话）嗜酸性粒细胞促进宿主防御。考虑到这一点，我们已经开始仔细研究嗜酸性粒细胞，哮喘和过敏性支气管痉挛，以及呼吸道病毒引起的疾病，特别是呼吸道合胞病毒（RSV）引起的疾病之间的一些有趣的联系。虽然嗜酸性粒细胞与支气管痉挛和组织损伤有关，因此被一致认为是RSV疾病的罪魁祸首，但我们已经开始考虑嗜酸性粒细胞炎症与呼吸道疾病的发生有关的可能性。双刃剑，？类似于在中性粒细胞中更仔细研究的结果。我们实验室最近的工作已经清楚地表明，嗜酸性粒细胞可以介导直接的，核糖核酸酶依赖性的RSV感染性的降低在体外，嗜酸性粒细胞分泌蛋白，嗜酸性粒细胞衍生的神经毒素（EDN/ RNase 2），可以单独作为一个独立的抗病毒剂。本提案中描述的实验将阐述嗜酸性粒细胞的生理学及其在宿主防御RSV中的作用，还将考虑EDN和相关核糖核酸酶作为抗病毒剂的药理学潜力和作用机制。- 嗜酸性粒细胞，宿主防御，核糖核酸酶，进化

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 reduction in infectivity 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. - Eosinophils, Host Defense, Ribonucleases, Evolution