OXIDATIVE EPITHELIAL DAMAGE PRODUCES HYPERRESPONSIVENESS OF HUMAN PERIPHERAL AIRWAYS
OXIDATIVE EPITHELIAL DAMAGE PRODUCES HYPERRESPONSIVENESS OF HUMAN PERIPHERAL AIRWAYS
复制标题
DOI：
10.1164/ajrccm.149.2.8306055
复制
发表时间：
1994-02-01
影响因子：
24.7
通讯作者：
DEJONGSTE, JC
中科院分区：
文献类型：
--
作者：
HULSMANN, AR;RAATGEEP, HR;DEJONGSTE, JC
上皮可能通过产生松弛因子、使激动剂失活或作为物理屏障来调节气道平滑肌的反应性。然而，在孤立的气道条，只有一个有限的调节作用的上皮细胞已被发现，这很可能是由于该气道模型的缺点。本研究比较了人气道导管和气道条中气道上皮的调节作用。此外，由于氧自由基可能有助于上皮细胞损伤哮喘，氧化损伤的气道上皮细胞诱导与管腔应用过氧化氢（H2 O2），并在反应性的变化，激动剂组胺，乙酰甲胆碱，和沙丁胺醇进行了测量。为了检查完整上皮是否作为组胺的屏障，在具有从粘膜侧刺激的完整和受损上皮的管中测量器官浴中的组胺浓度。在气道条中，未发现三种激动剂中任何一种在完整气道和上皮剥脱气道之间的反应性差异。相比之下，气道导管对组胺和乙酰甲胆碱的敏感性在粘膜刺激时显著低于血清刺激（-log EC（50）：组胺和乙酰甲胆碱分别为4.87和4.92对5.87和5.45，p < 0.001）。粘膜和血清刺激气道对沙丁胺醇的敏感性无差异（-log EC（50）：分别为6.19和6.20）。上皮细胞对收缩激动剂的敏感性的调节随着气道大小的增加而增加，并且在用H2 O2处理后被取消。H2 O2处理的气道制剂的光镜检查显示特定的损害柱状纤毛上皮细胞，与相对保存的基底细胞。组胺通过气道壁的渗透是相似的，在完整的和H2 O2处理的气道。这些结果表明，气道上皮的氧化损伤可能导致对吸入刺激的高反应性，然而，这可能不是由于受损上皮屏障功能的变化。
The epithelium probably modulates airway smooth muscle responsiveness by producing relaxing factors, by inactivating agonists, or by acting as a physical barrier. In isolated airway strips, however, only a limited modulatory role of the epithelium has been found, and this may well be due to shortcomings of this airway model. The present study compares the modulatory role of the airway epithelium in human airway tubes and strips. In addition, since oxygen radicals may contribute to epithelial damage in asthma, oxidative damage to the airway epithelium was induced with luminally applied hydrogen peroxide (H2O2), and changes in responsiveness to the agonists histamine, methacholine, and salbutamol were measured. To examine whether intact epithelium acts as a barrier to histamine, the histamine concentration in the organ bath was measured in tubes with intact and damaged epithelium stimulated from the mucosal side. In airway strips, no differences in responsiveness were found between intact and epithelium-denuded airways for any of the three agonists. In contrast, the sensitivity of airway tubes to both histamine and methacholine was significantly lower with mucosal stimulation than with serosal stimulation (-log EC(50): 4.87 and 4.92 versus 5.87 and 5.45 for histamine and methacholine, respectively, p < 0.001). No difference was found between the sensitivity to salbutamol of mucosally and serosally stimulated airways (-log EC(50): 6.19 and 6.20, respectively). The modulation of the sensitivity to contractile agonists by the epithelium increased with increasing airway size, and was abolished after treatment with H2O2. Light microscopic examination of H2O2-treated airway preparations revealed specific damage to the columnar ciliated epithelial cells, with relative preservation of basal cells. The penetration of histamine through the airway wall was similar in intact and H2O2-treated airways. These results suggest that oxidative damage to the airway epithelium may lead to hyperresponsiveness to inhaled stimuli; however, this may not be due to a change in barrier function of the damaged epithelium.