HUMAN PHAGOCYTE GRANULE PROTEINS

人类吞噬细胞颗粒蛋白

• 批准号: 6431620
• 负责人: HELENE ROSENBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431620
• 关键词: enzyme activity; eosinophil; glycoproteins; granule; human tissue; microorganism immunology; molecular cloning; neutrophil; pancreatic ribonuclease; protein biosynthesis; tissue /cell culture

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. We have extended these findings into an in vivo system using a mouse model of respiratory viral infection. Using a natural rodent pathogen, the paramyxovirus pneumonia virus of mice (PVM), we have identified pulmonary eosinophilia as a prominent early response to this infection, and we have identified MIP-1alpha as the primary chemokine responsible for the inflammatory response.

嗜酸性粒细胞是一种神秘的细胞，作为过敏性疾病和哮喘的介质具有明确的有害作用，而有益的特性仍然存在争议和知之甚少。事实上，鉴于最近的发现已经破坏了关于嗜酸性粒细胞作为体内抗寄生虫剂的假设，目前还不清楚嗜酸性粒细胞是如何促进宿主防御的（如果有的话）。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由呼吸道病毒引起的疾病，尤其是由呼吸道合胞病毒（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具有“双刃剑”的可能性，类似于在中性粒细胞中进行的更仔细的研究。我们实验室最近的工作清楚地表明，嗜酸性粒细胞可以介导体外RSV传染性的直接，核糖核酸酶依赖性降低，并且嗜酸性粒细胞分泌蛋白之一，嗜酸性粒细胞衍生神经毒素（EDN/ RNase 2）可以单独作为独立的抗病毒药物发挥作用。我们已经将这些发现扩展到使用呼吸道病毒感染小鼠模型的体内系统中。使用一种天然的啮齿动物病原体，小鼠副粘病毒肺炎病毒（PVM），我们已经确定肺嗜酸性粒细胞增生是对这种感染的突出早期反应，我们已经确定mip -1 α是负责炎症反应的主要趋化因子。