肥大细胞导致的气道结构改变参与了严重哮喘的致病过程
2011/05/11
摘要
过去，肥大细胞被认为是免疫系统的一种效应细胞。近期的研究显示，肥大细胞参与了哮喘和其他过敏性疾病的发生、发展和持续过程中的病理生理学过程。哮喘表现为气道炎症，同时伴随气道生理学功能的紊乱，如可逆性的气流受限和气道高反应(AHR)。有证据显示，肥大细胞通过与气道壁内的不同结构性成分之间形成紧密的细胞间联系，影响气道功能。在哮喘患者，肥大细胞位于气道的上皮、粘液腺和气道平滑肌(ASM)之间。肥大细胞-ASM之间的相互作用是哮喘表现型的主要基础，而且研究显示，许多肥大细胞介质能对ASM功能产生重要影响。对于哮喘患者，除了气道炎症和生理学改变外，还存在着气道壁的上皮细胞脱落、杯状细胞和粘液腺过度增生、上皮下纤维化、细胞外基质异常沉积、血管增殖和ASM增加等，这些最终导致气道结构的变化。肥大细胞可以通过直接的细胞-细胞间联系，也可通过释放细胞介质间接作用，导致上述气道的结构变化。肥大细胞具有多种生物学功能和作用，也是我们了解哮喘（特别是严重哮喘）发病机制的基础。针对肥大细胞及其介质的新作用靶位可能为哮喘提供重要的治疗手段。
（苏楠 审校）
Curr Pharm Des. 2011 Mar 15. [Epub ahead of print]
The Role of Mast Cells in the Structural Alterations of the Airways as a Potential Mechanism in the Pathogenesis of Severe Asthma.
Carter RJ, Bradding P.
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Clinical Sciences, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. rjfcarter@hotmail.com.
Abstract
Mast cells, traditionally regarded as effector cells of the immune system, have more recently been demonstrated to be key figures in initiating, developing and sustaining complex pathophysiological processes underlying asthma and other allergic diseases. Asthma is characterised by airway inflammation alongside a disturbance to airway physiology manifesting as variable airflow obstruction and airway hyper-responsiveness (AHR). Evidence has emerged that mast cells influence airway function by forming close intercellular relationships with different structural components of the airway wall. In asthma, mast cells are seen to localise to the airway epithelium, to mucous glands and to the airway smooth muscle (ASM). It is mast cell-ASM interaction that is most fundamental to the asthma phenotype and many mast cell mediators have been demonstrated to have important effects on ASM function. In asthma, alongside the inflammatory and physiological changes, structural changes occur to the airway wall in the form of as denudation of the epithelium, goblet cell and mucous gland hyperplasia, subepithelial fibrosis, abnormal extracellular matrix (ECM) deposition, vascular proliferation and increased ASM mass. There are many ways in which mast cells can contribute to these structural changes through direct cell to cell communication and more indirectly through mediator release. Mast cells exhibit an array of diverse functions and roles and are fundamental to our current understanding of asthma pathogenesis including severe asthma. Novel targeting of mast cells and their mediators therefore should offer significant therapeutic potential in the treatment of asthma.
Curr Pharm Des. 2011 Mar 15. [Epub ahead of print]
过去，肥大细胞被认为是免疫系统的一种效应细胞。近期的研究显示，肥大细胞参与了哮喘和其他过敏性疾病的发生、发展和持续过程中的病理生理学过程。哮喘表现为气道炎症，同时伴随气道生理学功能的紊乱，如可逆性的气流受限和气道高反应(AHR)。有证据显示，肥大细胞通过与气道壁内的不同结构性成分之间形成紧密的细胞间联系，影响气道功能。在哮喘患者，肥大细胞位于气道的上皮、粘液腺和气道平滑肌(ASM)之间。肥大细胞-ASM之间的相互作用是哮喘表现型的主要基础，而且研究显示，许多肥大细胞介质能对ASM功能产生重要影响。对于哮喘患者，除了气道炎症和生理学改变外，还存在着气道壁的上皮细胞脱落、杯状细胞和粘液腺过度增生、上皮下纤维化、细胞外基质异常沉积、血管增殖和ASM增加等，这些最终导致气道结构的变化。肥大细胞可以通过直接的细胞-细胞间联系，也可通过释放细胞介质间接作用，导致上述气道的结构变化。肥大细胞具有多种生物学功能和作用，也是我们了解哮喘（特别是严重哮喘）发病机制的基础。针对肥大细胞及其介质的新作用靶位可能为哮喘提供重要的治疗手段。
（苏楠 审校）
Curr Pharm Des. 2011 Mar 15. [Epub ahead of print]
The Role of Mast Cells in the Structural Alterations of the Airways as a Potential Mechanism in the Pathogenesis of Severe Asthma.
Carter RJ, Bradding P.
Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Clinical Sciences, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK. rjfcarter@hotmail.com.
Abstract
Mast cells, traditionally regarded as effector cells of the immune system, have more recently been demonstrated to be key figures in initiating, developing and sustaining complex pathophysiological processes underlying asthma and other allergic diseases. Asthma is characterised by airway inflammation alongside a disturbance to airway physiology manifesting as variable airflow obstruction and airway hyper-responsiveness (AHR). Evidence has emerged that mast cells influence airway function by forming close intercellular relationships with different structural components of the airway wall. In asthma, mast cells are seen to localise to the airway epithelium, to mucous glands and to the airway smooth muscle (ASM). It is mast cell-ASM interaction that is most fundamental to the asthma phenotype and many mast cell mediators have been demonstrated to have important effects on ASM function. In asthma, alongside the inflammatory and physiological changes, structural changes occur to the airway wall in the form of as denudation of the epithelium, goblet cell and mucous gland hyperplasia, subepithelial fibrosis, abnormal extracellular matrix (ECM) deposition, vascular proliferation and increased ASM mass. There are many ways in which mast cells can contribute to these structural changes through direct cell to cell communication and more indirectly through mediator release. Mast cells exhibit an array of diverse functions and roles and are fundamental to our current understanding of asthma pathogenesis including severe asthma. Novel targeting of mast cells and their mediators therefore should offer significant therapeutic potential in the treatment of asthma.
Curr Pharm Des. 2011 Mar 15. [Epub ahead of print]
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过敏性哮喘中尿酸作为针对吸入性抗原和炎症介质的Th2细胞免疫的诱导子
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2个出生队列研究（ALSPAC和PIAMA）中儿童喘息表现型的比较
