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肺部疾病中的黏附分子。

Adhesion molecules in lung diseases.

作者信息

Hamacher J, Schaberg T

机构信息

Department of Pulmonary Medicine, Chest Hospital Heckeshorn-Zehlendorf Zum Heckeshorn, Berlin, Germany.

出版信息

Lung. 1994;172(4):189-213. doi: 10.1007/BF00164437.

Abstract

The human body possesses highly specialized cellular defense mechanisms that, when activated pathologically, can induce a number of immunologic disorders. For a normal cellular immune response, the following conditions must be fulfilled: (1) accumulation of white blood cells, (2) their diapedesis through the vessel walls of the inflammatory area affected by an injurious agent, and (3) normal cellular effector functions in the tissue. This cascade of inflammatory processes has recently been shown to be regulated by a group of molecules that are termed adhesion molecules and consist of three subfamilies: selectins, the immunoglobulin supergene family, and integrins. The cellular functions influenced by adhesion molecules include, among others, cytotoxic T-cell responses, CD4-dependent activation of B lymphocytes by T lymphocytes, activation of granulocytes and macrophages, phagocytosis of opsonized particles by monocytes, macrophages, and granulocytes, antigen-presenting function of macrophages, their antibody-dependent cytotoxicity, initiation of a respiratory burst by white blood cells, and activation of fibroblasts. Studies performed in recent years have shown that pathogenetically relevant changes in the expression and function of adhesion molecules are involved in a variety of pulmonary diseases. These changes include the accumulation and activation of alveolar macrophages in smokers, experimentally induced bronchial hyperreactivity in bronchial asthma, accumulation of eosinophils in allergic rhinitis, bleomycin-induced pulmonary fibrosis, binding of viruses and bacteria to respiratory mucosa, and various mechanisms of acute damage to pulmonary parenchyma. Though their role in tumor development is still unclear, adhesion molecules are obviously involved in determining the route and organotropism of metastases. Further studies of the function of adhesion molecules in pulmonary diseases will contribute to our understanding of the pathomechanisms of these diseases and, through the development of specific antibodies, may provide attractive new therapeutic approaches to problems for which treatment is not yet available.

摘要

人体拥有高度专业化的细胞防御机制,当这些机制发生病理性激活时,可诱发多种免疫紊乱。对于正常的细胞免疫反应,必须满足以下条件:(1)白细胞的聚集;(2)它们通过受损伤因子影响的炎症区域的血管壁渗出;(3)组织中正常的细胞效应功能。最近已表明,这一连串的炎症过程受一组称为黏附分子的分子调节,黏附分子由三个亚家族组成:选择素、免疫球蛋白超基因家族和整合素。受黏附分子影响的细胞功能包括细胞毒性T细胞反应、T淋巴细胞对B淋巴细胞的CD4依赖性激活、粒细胞和巨噬细胞的激活、单核细胞、巨噬细胞和粒细胞对调理素化颗粒的吞噬作用、巨噬细胞的抗原呈递功能、其抗体依赖性细胞毒性、白细胞引发的呼吸爆发以及成纤维细胞的激活等。近年来进行的研究表明,黏附分子表达和功能的致病性相关变化涉及多种肺部疾病。这些变化包括吸烟者肺泡巨噬细胞的聚集和激活、实验性诱导的支气管哮喘中的支气管高反应性、过敏性鼻炎中嗜酸性粒细胞的聚集、博来霉素诱导的肺纤维化、病毒和细菌与呼吸道黏膜的结合以及肺实质急性损伤的各种机制。尽管黏附分子在肿瘤发展中的作用仍不清楚,但它们显然参与了转移途径和器官嗜性的确定。对黏附分子在肺部疾病中功能的进一步研究将有助于我们理解这些疾病的发病机制,并且通过开发特异性抗体,可能为尚无有效治疗方法的问题提供有吸引力的新治疗途径。

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