Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
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DOI：
10.1164/rccm.200603-392oc
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发表时间：
2006-11-15
影响因子：
24.7
通讯作者：
Stick, Stephen M.
中科院分区：
文献类型：
--
作者：
Kicic, Anthony;Sutanto, Erika N.;Stick, Stephen M.
理论基础：即使在没有炎症的情况下，成人哮喘的呼吸道也存在令人信服的上皮损伤和异常修复的证据。目的：探讨哮喘患儿的支气管上皮细胞是否与非哮喘患儿的支气管上皮细胞有本质的区别。方法：通过非支气管镜下刷检获得轻度哮喘患儿(n=7)、特应性哮喘患儿(n=9)和健康儿童(n=12)的支气管上皮细胞。对细胞进行形态、生化、分子和功能评价。结果：所有的上皮细胞均呈“鹅卵石”状，在整个培养和重复传代过程中一直保持这种形态。细胞角蛋白19的表达各不相同，疾病表型在健康的非特应性哮喘患者中最多，在哮喘患者中最低。相反，细胞角蛋白5/14在哮喘样本中表达最多，在健康非特应性样本中表达最少。哮喘上皮细胞自发产生的IL-6、前列腺素E-2和表皮生长因子显著增多，IL-1β和可溶性细胞间黏附分子-1显著增加，而转化生长因子β1显著降低。哮喘患儿肺上皮细胞的增殖率也高于非哮喘患儿。结论：轻度哮喘患儿的上皮细胞与非哮喘患儿的上皮细胞在生化和功能上存在本质差异。重要的是，这些差异在连续的传代中保持不变，这表明它们不依赖于体内环境。
Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways, even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples.Objectives: To determine whether bronchial epithelial cells from children with asthma are inherently distinct from those obtained from children without asthma.Methods: Epithelial cells were obtained by nonbronchoscopic bronchial brushing of children with mild asthma (n = 7), atopic children without asthma (n = 9), and healthy children (n = 12). Cells were subject to morphologic, biochemical, molecular, and functional assessment. Responses were also compared with commercially available epithelial cultures and the transformed cell line 16HBE140.Results: All epithelial cells exhibited a "cobblestone" morphology, which was maintained throughout culture and repeated passage. Expression of cytokeratin 19 varied, with disease phenotype being greatest in healthy nonatopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatic samples and least in healthy nonatopic samples. Asthmatic epithelial cells also spontaneously produced significantly greater amounts of interleukin (IL)-6, prostaglandin E-2, and epidermal growth factor, and equivalent amounts of IL-1 beta and soluble intracellular adhesion molecule-1, but significantly lower amounts of transforming growth factor beta 1. This profile was maintained through successive passages. Asthmatic epithelial cells also exhibited greater rates of proliferation than nonasthmatic cells.Conclusions: This study has shown that epithelial cells from children with mild asthma are intrinsically different both biochemically and functionally compared with epithelial cells from children without asthma. Importantly, these differences are maintained over successive passages, suggesting that they are not dependent on an in vivo environment.