The role of the mast cell in the pathophysiology of asthma
The role of the mast cell in the pathophysiology of asthma
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DOI：
10.1016/j.jaci.2006.02.039
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发表时间：
2006-06-01
影响因子：
14.2
通讯作者：
Holgate, ST
中科院分区：
文献类型：
--
作者：
Bradding, P;Walls, AF;Holgate, ST
有令人信服的证据表明，人类肥大细胞有助于哮喘的病理生理学。肥大细胞，而不是T细胞或嗜酸性粒细胞，定位于支气管平滑肌束在哮喘患者，但不是在正常受试者或那些与嗜酸性支气管炎，一个因素可能是重要的，在确定哮喘表型。哮喘气道平滑肌募集肥大细胞的机制涉及CXCL 10/CXCR 3轴，并且一些肥大细胞介质对气道平滑肌功能有着深远的影响。自泌素被确定为有效的支气管收缩剂，而蛋白酶类胰蛋白酶和糜蛋白酶被证明具有一系列与炎症、组织重塑和支气管高反应性中的关键作用一致的作用。IL-4和IL-13，已知的肥大细胞产物，也诱导小鼠的支气管高反应性，与炎症反应无关，并增强激动剂诱导的培养的人气道平滑肌细胞内Ca 2+反应的幅度。因此，有许多途径，肥大细胞与气道平滑肌细胞的密切接近可能导致气道平滑肌功能紊乱。哮喘患者气道粘液腺中也有肥大细胞浸润，表现为脱颗粒特征，且与粘液阻塞气道腔的程度呈正相关，提示肥大细胞在调节粘液腺分泌中起重要作用。肥大细胞分泌的有效和特异性抑制剂的开发，长期给药哮喘气道时保持活性，应该提供一种新的方法来治疗哮喘。
There is compelling evidence that human mast cells contribute to the pathophysiology of asthma. Mast cells, but not T cells or eosinophils, localize within the bronchial smooth muscle bundles in patients with asthma but not in normal subjects or those with eosinophilic bronchitis, a factor likely to be important in determining the asthmatic phenotype. The mechanism of mast cell recruitment by asthmatic airway smooth muscle involves the CXCL10/CXCR3 axis, and several mast cell mediators have profound effects on airway smooth muscle function. The autacoids are established as potent bronchoconstrictors, whereas the proteases tryptase and chymase are being demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodeling, and bronchial hyperresponsiveness. IL-4 and IL-13, known mast cell products, also induce bronchial hyperresponsiveness in the mouse independent of the inflammatory response and enhance the magnitude of agonist-induced intracellular Ca2+ responses in cultured human airway smooth muscle. There are therefore many pathways by which the close approximation of mast cells with airway smooth muscle cells might lead to disordered airway smooth muscle function. Mast cells also infiltrate the airway mucous glands in subjects with asthma, showing features of degranulation, and a positive correlation with the degree of mucus obstructing the airway lumen, suggesting that mast cells play an important role in regulating mucous gland secretion. The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma.