Experimental Pneumology, Research Center Borstel, Parkallee 1, D-23845 Borstel, Germany 1887402.
Am J Respir Cell Mol Biol. 2011 Oct;45(4):667-74. doi: 10.1165/rcmb.2011-0013TR. Epub 2011 Apr 7.
Due to their role as main effector cells in immune reactions against invading parasites, eosinophils have a plethora of molecules available to destroy these complex pathogens. Their role in allergic diseases such as bronchial asthma, where they do not have to conquer pathogens, is discussed controversially. However, since eosinophils were identified by Paul Ehrlich in tissue and sputum of patients with asthma, it was regarded that their important defensive role turns into its direct opposite so that these cells cause destruction of the airway tissue, ultimately leading to the formation of disease phenotype. Thus, eosinophils were identified as a prime target in therapeutic intervention of bronchial asthma. Over the last years, a number of mediators and receptors involved in the regulation of eosinophil recruitment, chemotaxis, activation, survival, and apoptosis have been identified. Some of these molecules have been addressed in vitro and in animal models of experimental asthma to evaluate their therapeutic potential in asthma. A few of these candidates have been tested in clinical studies, which produced surprising results questioning the role of eosinophils in asthma pathogenesis. This article summarizes these approaches and gives a critical overview about further candidate molecules that have been recently discussed as targets for an eosinophil-specific asthma therapy.
由于嗜酸性粒细胞在免疫反应中作为主要效应细胞对抗入侵的寄生虫，因此它们有大量的分子可用于破坏这些复杂的病原体。它们在支气管哮喘等过敏性疾病中的作用存在争议，在哮喘患者的组织和痰液中，嗜酸性粒细胞是由保罗·埃尔利希（Paul Ehrlich）发现的，人们认为它们的重要防御作用变成了直接相反的作用，即这些细胞导致气道组织的破坏，最终导致疾病表型的形成。因此，嗜酸性粒细胞被确定为支气管哮喘治疗干预的主要靶点。近年来，已经鉴定出许多参与嗜酸性粒细胞募集、趋化、激活、存活和凋亡调节的介质和受体。其中一些分子已在体外和实验性哮喘的动物模型中进行了研究，以评估它们在哮喘中的治疗潜力。其中一些候选药物已在临床研究中进行了测试，这些结果出人意料地质疑了嗜酸性粒细胞在哮喘发病机制中的作用。本文总结了这些方法，并对最近被认为是嗜酸性粒细胞特异性哮喘治疗靶点的其他候选分子进行了批判性概述。
