Rosenberg H F, Domachowske J B
Eosinophil Biology Unit, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Leukoc Biol. 2001 Nov;70(5):691-8.
Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities--e.g., asthma and allergic disease--far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword.
嗜酸性粒细胞仍然是最神秘的细胞之一，因为我们对其有害活动（如哮喘和过敏性疾病）的认识远远超过了对其有益作用的理解。在嗜酸性粒细胞的主要分泌效应蛋白中，灵长类动物的核糖核酸酶嗜酸性粒细胞衍生神经毒素（EDN）和嗜酸性粒细胞阳离子蛋白（ECP）及其直系同源物，啮齿动物中的嗜酸性粒细胞相关核糖核酸酶（EARs）。在这些核糖核酸酶中观察到的快速多样化表明，最终靶标可能同样有效地产生序列多样性，同时保持对核糖核酸酶切割的不变敏感性。这促使我们考虑这些蛋白质以及嗜酸性粒细胞在宿主防御单链RNA病毒病原体中的作用。我们详细介绍了嗜酸性粒细胞和嗜酸性粒细胞核糖核酸酶在体外对呼吸道合胞病毒（RSV）以及在体内对相关的天然啮齿动物病原体小鼠肺炎病毒（PVM）的抗病毒活性研究，并考虑了抗病毒宿主防御和导致哮喘的失调反应代表嗜酸性粒细胞介导的双刃剑的相反两面的可能性。
