Department of Otolaryngology, SUNY Upstate Medical University, Syracuse, NY.
Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL.
Int Forum Allergy Rhinol. 2018 Apr;8(4):509-512. doi: 10.1002/alr.22065. Epub 2018 Jan 10.
Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS.
Mucosal explants from patients with and without CRS were submerged in Ringer's solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of Z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plug-in of ImageJ.
Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53 ± 0.67 vs controls, 4.86 ± 1.68 pixels/second; p < 0.001).
This study is the first to report evidence of abnormal mucus strand velocity from submucosal glands in diseased sinonasal mucosa. Future pharmacologic studies targeting this critical component of MCC are warranted.
慢性鼻-鼻窦炎(CRS)可能由先天受损的宿主防御机制引起,使上呼吸道易受感染。最近的证据表明,粘蛋白链在囊性纤维化(CF)气道中的固定是一个激发事件,发生在慢性感染之前。粘膜下腺肥大和纤毛粘液清除功能(MCC)缺陷存在于活跃炎症的鼻窦中,但粘蛋白链速度也可能受到影响,作为二次事件,进一步导致慢性疾病。本研究的目的是评估粘液链速度是否在 CRS 患者中降低。
将有和没有 CRS 的患者的粘膜外植体浸入含荧光纳米球的林格氏溶液中。然后加入乙酰甲胆碱,使用多光子共聚焦显微镜对 Z 堆叠图像的延时拍摄生成显示链生长和分离的视频。使用 ImageJ 的 MTrackJ 插件识别动态粘液链并量化个体速度。
15 名患者符合粘液链速度的体外分析标准(CRS,n=9 与对照,n=6)。从粘膜下腺开口记录粘液链(像素/秒)的流动。CRS 患者的平均粘液链速度明显降低(1.53 ± 0.67 与对照,4.86 ± 1.68 像素/秒;p<0.001)。
这项研究首次报道了病变鼻-鼻窦粘膜中粘膜下腺异常粘液链速度的证据。未来有必要针对 MCC 的这一关键组成部分进行靶向药物治疗的药理学研究。