Reversal of chronic rhinosinusitis-associated sinonasal ciliary dysfunction
Reversal of chronic rhinosinusitis-associated sinonasal ciliary dysfunction
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DOI：
10.2500/ajr.2007.21.3029
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发表时间：
2007-05-01
期刊：
影响因子：
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通讯作者：
Cohen, Noam A.
中科院分区：
文献类型：
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作者：
Chen, Bei;Antunes, Marcelo B.;Cohen, Noam A.
背景资料：虽然多种病因导致慢性鼻窦炎（CRS）的发展，但常见的病理生理学后遗症是鼻窦粘膜纤毛清除无效，导致鼻窦分泌物停滞，随后发生感染和/或持续性炎症。适当的治疗干预通常会恢复粘膜纤毛活性，这表明导致CRS相关粘膜停滞的病理生理过程可能是可逆的。我们以前证明了一个钝的反应后，CRS鼻窦纤毛嘌呤刺激。这项研究调查了钝纤毛反应是否是唯一的嘌呤能刺激，并解决了钝效应是否主要是由局部CRS相关介质或先天遗传缺陷的纤毛功能。使用双温度控制灌注室、微分干涉对比显微镜和高速数字视频来分析基础以及胆碱能、肾上腺素能、和嘌呤能刺激人鼻窦粘膜外植体中的纤毛。此外，酶解离的鼻窦纤毛细胞保持离体浸没，盖玻片上，并每天评估嘌呤能纤毛拍频stimulation.Results：胆碱能和肾上腺素能刺激一般钝化从CRS患者的粘膜外植体。离体维护的样品表明，大多数CRS样品开发的刺激表型在36小时内culture.Conclusion：CRS是一种常见的衰弱性疾病，主要影响鼻窦上皮功能，从而减少粘液纤毛运输。目前，很少有人知道这种疾病的过程中如何影响鼻窦上皮纤毛细胞。我们的数据表明，在CRS患者中，睫状体对环境损伤的反应是可逆的。
Background: Although multiple etiologies contribute to the development of chronic rhinosinusitis (CRS), a common pathophysiological sequelae is ineffective sinonasal mucociliary clearance, leading to stasis of sinonasal secretions, with subsequent infection and/or persistent inflammation. Proper therapeutic intervention typically restores mucociliary activity, suggesting that the pathophysiological process(es) responsible for CRS-associated mucostasis may be reversible. We previously demonstrated a blunted response of CRS sinonasal cilia after purinergic stimulation. This study investigated whether the blunted ciliary response is unique to purinergic stimulation and addressed whether the blunted effect is primarily caused by local CRS-associated mediators or inherent genetic defects in ciliary function.Methods: A dual tempera tu re-con trolled perfusion chamber, differential interference contrast microscopy, and high-speed digital video were used to analyze both basal as well as cholinergic, adrenergic, and purinergic stimulation of cilia in human sinonasal mucosal explants. Additionally, enzymically dissociated sinonasal ciliated cells were maintained ex vivo in submersion, on glass coverslips, and assessed daily for purinergic ciliary beat frequency stimulation.Results: Cholinergic and adrenergic stimulation generally were blunted in mucosal explants obtained from CRS patients. Ex vivo maintenance of samples demonstrated that the majority of CRS samples developed a stimulatory phenotype within 36 hours of culturing.Conclusion: CRS is a common debilitating disease principally affecting sinonasal epithelial function with a resultant diminution of mucociliary transport. Presently, little is known about how this disease process affects the sinonasal epithelial ciliated cells. Our data suggest that ciliary response to environmental insults is blunted in a reversible manner in CRS patients.