HUMAN PHAGOCYTE GRANULE PROTEINS

嗜酸性粒细胞是一种神秘的细胞，具有作为变态反应性疾病和哮喘的媒介的有害作用，以及仍然存在争议和鲜为人知的有益特征。事实上，鉴于最近的发现削弱了体内嗜酸性粒细胞作为抗寄生虫剂的假说，根本不清楚嗜酸性粒细胞在促进宿主防御方面起到了什么作用(如果有的话)。考虑到这一点，我们已经开始仔细研究一些有趣的关联，它们将嗜酸性粒细胞、哮喘和过敏性支气管痉挛与呼吸道病毒引起的疾病联系起来，最明显的是由呼吸道合胞病毒(RSV)引起的疾病。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这样一种可能性，即嗜酸性粒细胞炎症有一把“双刃剑”，类似于对中性粒细胞的更仔细研究。我们实验室最近的工作清楚地表明，嗜酸性粒细胞在体外可以直接介导依赖核糖核酸酶的RSV感染性降低，并且嗜酸性粒细胞分泌蛋白之一--嗜酸性粒细胞衍生的神经毒素(EDN/RNase2)可以单独作为独立的抗病毒药物发挥作用。我们利用呼吸道病毒感染的小鼠模型，将这些发现扩展到体内系统。利用一种天然的啮齿动物病原体--小鼠副粘病毒肺炎病毒(PVM)，我们发现肺嗜酸性粒细胞增多是这种感染的早期显著反应，我们已经确定MIP-1α是导致炎症反应的主要趋化因子。

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.