Knight Darryl A, Holgate Stephen T
Asthma and Allergy Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Respirology. 2003 Dec;8(4):432-46. doi: 10.1046/j.1440-1843.2003.00493.x.
The major function of the respiratory epithelium was once thought to be that of a physical barrier. However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. It also responds to changes in the external environment by secreting a large number of molecules and mediators that signal to cells of the immune system and underlying mesenchyme. Thus, the epithelium is in a unique position to translate gene-environment interactions. Normally, the epithelium has a tremendous capacity to repair itself following injury. However, evidence is rapidly accumulating to show that the airway epithelium of asthmatics is abnormal and has increased susceptibility to injury compared to normal epithelium. Areas of detachment and fragility are a characteristic feature not observed in other inflammatory diseases such as COPD. In addition to being more susceptible to damage, normal repair processes are also compromised. Failure of appropriate growth and differentiation of airway epithelial cells will cause persistent mucosal injury. The response to traditional therapy such as glucocorticoids may also be compromised. However, whether the differences observed in asthmatic epithelium are a cause of or secondary to the development of the disease remains unanswered. Strategies to address this question include careful examination of the ontogeny of the disease in children and use of gene array technology should provide some important answers, as well as allow a better understanding of the critical role that the epithelium plays under normal conditions and in diseases such as asthma.
呼吸上皮的主要功能曾被认为是作为一种物理屏障。然而,它构成了内部环境与外部环境之间的界面,同时也是吸入性呼吸药物的主要作用靶点。它还通过分泌大量向免疫系统细胞和下方间充质发出信号的分子和介质来响应外部环境的变化。因此,上皮细胞处于一个独特的位置来转化基因 - 环境相互作用。正常情况下,上皮细胞在损伤后具有巨大的自我修复能力。然而,越来越多的证据表明,与正常上皮相比,哮喘患者的气道上皮是异常的,并且对损伤更敏感。脱落和脆弱区域是慢性阻塞性肺疾病等其他炎症性疾病中未观察到的特征性表现。除了更容易受到损伤外,正常的修复过程也受到损害。气道上皮细胞的生长和分化异常会导致持续性的黏膜损伤。对糖皮质激素等传统治疗的反应也可能受到影响。然而,哮喘上皮中观察到的差异是疾病发生的原因还是疾病发展的结果仍未得到解答。解决这个问题的策略包括仔细研究儿童疾病的发生过程,使用基因芯片技术应该能提供一些重要答案,同时也能更好地理解上皮细胞在正常情况下以及在哮喘等疾病中所起的关键作用。