针对嗜酸粒细胞生物学的哮喘治疗方法
2011/06/17
摘要
嗜酸粒细胞是体内针对入侵的寄生虫产生免疫反应的主要效应细胞，能产生大量的分子摧毁入侵的病原体。这些嗜酸粒细胞在过敏性疾病（如支气管哮喘，此时嗜酸粒细胞不起到破坏病原体的作用）中的作用存在争论。Paul Ehrlich 已经在哮喘患者的组织和痰液中发现有嗜酸性粒细胞存在，因此，认为嗜酸粒细胞的作用从原有的防御性表现转为对组织的破坏，这些细胞可能会导致气道组织的破坏，从而形成疾病的表现型。因此，嗜酸粒细胞可以作为支气管哮喘治疗的主要靶点。过去几年中，许多介质和受体被发现参与了嗜酸粒细胞募集、趋化、活化、生存和凋亡的调节。一些体内或动物模型研究中，对某些分子在治疗哮喘中的作用进行了评价。此外，某些临床试验也对其中的某些分子在哮喘治疗中的作用进行了研究，但是所得到的结果有些令人费解，仍然未阐明嗜酸性粒细胞在哮喘致病中的作用。本文旨在对这些方法进行总结，并对近期嗜酸性粒细胞特异性哮喘治疗的靶点进行讨论。
（林江涛 审校）
Am J Respir Cell Mol Biol. 2011 Apr 7. [Epub ahead of print]
Targeting Eosinophil’s Biology in Asthma Therapy.
Wegmann M.
Dept. of Experimental Pneumology, Research Center Borstel, Parkallee 1-40, Borstel, 23845, Germany.
Abstract
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 these do not have to controvert pathogens, is discussed controversially. However, ever since eosinophils have been identified by Paul Ehrlich in tissue and sputum of asthma patients, 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. Furthermore, the therapeutic potential of a few of these candidates has been evaluated in clinical studies, which produced quite perplexing results that even questioned the role of eosinophils in asthma pathogenesis. This article aims at summarizing these approaches and gives a critical overview about further candidate molecules that are recently discussed as targets for an eosinophil specific asthma therapy.
Am J Respir Cell Mol Biol. 2011 Apr 7. [Epub ahead of print]
嗜酸粒细胞是体内针对入侵的寄生虫产生免疫反应的主要效应细胞，能产生大量的分子摧毁入侵的病原体。这些嗜酸粒细胞在过敏性疾病（如支气管哮喘，此时嗜酸粒细胞不起到破坏病原体的作用）中的作用存在争论。Paul Ehrlich 已经在哮喘患者的组织和痰液中发现有嗜酸性粒细胞存在，因此，认为嗜酸粒细胞的作用从原有的防御性表现转为对组织的破坏，这些细胞可能会导致气道组织的破坏，从而形成疾病的表现型。因此，嗜酸粒细胞可以作为支气管哮喘治疗的主要靶点。过去几年中，许多介质和受体被发现参与了嗜酸粒细胞募集、趋化、活化、生存和凋亡的调节。一些体内或动物模型研究中，对某些分子在治疗哮喘中的作用进行了评价。此外，某些临床试验也对其中的某些分子在哮喘治疗中的作用进行了研究，但是所得到的结果有些令人费解，仍然未阐明嗜酸性粒细胞在哮喘致病中的作用。本文旨在对这些方法进行总结，并对近期嗜酸性粒细胞特异性哮喘治疗的靶点进行讨论。
（林江涛 审校）
Am J Respir Cell Mol Biol. 2011 Apr 7. [Epub ahead of print]
Targeting Eosinophil’s Biology in Asthma Therapy.
Wegmann M.
Dept. of Experimental Pneumology, Research Center Borstel, Parkallee 1-40, Borstel, 23845, Germany.
Abstract
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 these do not have to controvert pathogens, is discussed controversially. However, ever since eosinophils have been identified by Paul Ehrlich in tissue and sputum of asthma patients, 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. Furthermore, the therapeutic potential of a few of these candidates has been evaluated in clinical studies, which produced quite perplexing results that even questioned the role of eosinophils in asthma pathogenesis. This article aims at summarizing these approaches and gives a critical overview about further candidate molecules that are recently discussed as targets for an eosinophil specific asthma therapy.
Am J Respir Cell Mol Biol. 2011 Apr 7. [Epub ahead of print]
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吸烟哮喘患者短期阿伐他汀治疗的疗效---随机对照试验
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严重哮喘的激素抵抗：当前的机制研究和未来的治疗方向
