Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair.
Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair.
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DOI：
10.1165/rcmb.2008-0009oc
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发表时间：
2008-09
影响因子：
6.4
通讯作者：
K. Oslund;D. Hyde;L. Putney;M. F. Alfaro;W. Walby;N. Tyler;E. Schelegle
中科院分区：
文献类型：
--
作者：
K. Oslund;D. Hyde;L. Putney;M. F. Alfaro;W. Walby;N. Tyler;E. Schelegle
我们研究了神经激肽（NK）-1受体在上皮损伤和修复以及中性粒细胞功能中的重要性。清醒的Wistar大鼠暴露于1 ppm的臭氧或过滤空气8小时，然后是8小时的postextraximation期。在暴露前，我们给予NK-1受体拮抗剂SR140333或生理盐水作为对照。向肺中滴入异二聚体，作为坏死气道上皮细胞的标志物。固定后，对整个气道解剖的肺叶进行5-溴-2'-脱氧尿苷免疫染色，5-溴-2'-脱氧尿苷是上皮增殖的标志物。在特定的气道世代中对乙锭同二聚体和5-溴-2'-脱氧尿苷阳性上皮细胞进行定量。与对照组大鼠相比，NK-1受体拮抗剂治疗的大鼠上皮损伤和上皮增殖显著减少。终末细支气管切片显示两组气道中中性粒细胞数量无显著差异。此外，染色臭氧暴露的肺切片的活性半胱天冬酶3显示没有凋亡细胞，但乙锭阳性细胞与孤儿核受体Nur77共定位，Nur77是NK-1受体介导的非凋亡，程序性细胞死亡的标志物。永生化人气道上皮细胞系人支气管上皮-1在暴露于过氧化氢和一系列SR 140333剂量期间，氧化应激阳性细胞数量无显著差异，表明受体拮抗剂无抗氧化作用。我们得出结论，急性臭氧吸入过程中NK-1受体的激活有助于上皮损伤和随后的上皮增殖，修复的关键组成部分，但不影响中性粒细胞迁移到气道。
We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-2'-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stress-positive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.