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Chemokines: structure receptors and functions. A new target for inflammation and asthma therapy?

机译:趋化因子:结构受体和功能。炎症和哮喘治疗的新目标?

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摘要

Five to 10% of the human population have a disorder of the respiratory tract called ‘asthma’. It has been known as a potentially dangerous disease for over 2000 years, as it was already described by Hippocrates and recognized as a disease entity by Egyptian and Hebrew physicians. At the beginning of this decade, there has been a fundamental change in asthma management. The emphasis has shifted from symptom relief with bronchodilator therapies (e.g. β2-agonists) to a much earlier introduction of anti-inflammatory treatment (e.g. corticosteroids). Asthma is now recognized to be a chronic inflammatory disease of the airways, involving various inflammatory cells and their mediators. Although asthma has been the subject of many investigations, the exact role of the different inflammatory cells has not been elucidated completely. Many suggestions have been made and several cells have been implicated in the pathogenesis of asthma, such as the eosinophils, the mast cells, the basophils and the lymphocytes. To date, however, the relative importance of these cells is not completely understood. The cell type predominantly found in the asthmatic lung is the eosinophil and the recruitment of these eosinophils can be seen as a characteristic of asthma. In recent years much attention is given to the role of the newly identified chemokines in asthma pathology. Chemokines are structurally and functionally related 8–10 kDa peptides that are the products of distinct genes clustered on human chromosomes 4 and 17 and can be found at sites of inflammation. They form a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and lymphocytes. The chemokine superfamily can be divided into three subgroups based on overall sequence homology. Although the chemokines have highly conserved amino acid sequences, each of the chemokines binds to and induces the chemotaxis of particular classes of white blood cells. Certain chemokines stimulate the recruitment of multiple cell types including monocytes, lymphocytes, basophils, and eosinophils, which are important cells in asthma. Intervention in this process, by the development of chemokine antagonists, might be the key to new therapy. In this review we present an overview of recent developments in the field of chemokines and their role in inflammations as reported in literature.
机译:人口中有5至10%患有称为“哮喘”的呼吸道疾病。正如希波克拉底已经描述的那样,它已经被公认为有潜在危险的疾病超过2000年,并被埃及和希伯来医师确认为疾病实体。在这十年的开始,哮喘管理发生了根本性的变化。重点已经从使用支气管扩张剂疗法缓解症状(例如β2受体激动剂)转移到更早采用抗炎治疗方法(例如皮质类固醇)。现在公认哮喘是气道的慢性炎性疾病,涉及多种炎性细胞及其介体。尽管哮喘已成为许多研究的主题,但尚未完全阐明不同炎症细胞的确切作用。已经提出了许多建议,并且已经将几种细胞与哮喘的发病机理联系起来,例如嗜酸性粒细胞,肥大细胞,嗜碱性粒细胞和淋巴细胞。但是,到目前为止,还没有完全了解这些电池的相对重要性。主要在哮喘的肺中发现的细胞类型是嗜酸性粒细胞,这些嗜酸性粒细胞的募集可以看作是哮喘的特征。近年来,人们对新发现的趋化因子在哮喘病理中的作用给予了极大关注。趋化因子是与结构和功能相关的8–10 kDa肽,是在人类4号和17号染色​​体上簇集的不同基因的产物,可以在炎症部位发现。它们形成促炎介质的超家族,其促进各种白细胞和淋巴细胞的募集。基于整体序列同源性,趋化因子超家族可分为三个亚组。尽管趋化因子具有高度保守的氨基酸序列,但是每种趋化因子结合并诱导特定类别的白细胞的趋化性。某些趋化因子刺激多种细胞类型的募集,包括单核细胞,淋巴细胞,嗜碱性粒细胞和嗜酸性粒细胞,它们是哮喘中的重要细胞。通过趋化因子拮抗剂的开发干预这一过程可能是新疗法的关键。在这篇综述中,我们概述了趋化因子领域的最新发展及其在炎症中的作用,如文献报道。

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