Department of Medicine, McMaster University, Hamilton, ON, Canada.
J Aerosol Med Pulm Drug Deliv. 2012 Apr;25(2):88-95. doi: 10.1089/jamp.2011.0914. Epub 2012 Jan 26.
Inhalation of hypertonic saline and mannitol improve mucociliary clearance in patients with bronchiectasis, but little is known about how the relative osmotic strengths of these compounds affect ciliary beat frequency (CBF) of ciliated human bronchial epithelial cells (HBEC). Our aim was to compare in vitro the direct effects of osmotically equivalent solutions on CBF of HBEC.
HBEC were acutely (10, 30 min) exposed to comparable osmolar solutions of saline (0.03-0.48%), mannitol (0.19-3%) and dextran (10%-39.39%). Effects of higher % solutions, reversibility of responses, and prolonged treatments (15-20 h) were also compared. CBF was measured using digital videomicroscopy at baseline and at all time points.
CBF of HBEC increased significantly after acute exposure to mannitol (0.19%, 0.38%), decreased with dextran and remained unchanged with saline. Prolonged exposure to mannitol at high (3%, 6%) osmolar concentrations reversibly suppressed CBF. In comparison, acute and prolonged treatment with 39.39% dextran (equivalent to 3% mannitol) reduced CBF irreversibly. Furthermore, acute and prolonged treatment with 1% saline (equivalent to 6% mannitol) suppressed CBF with only the acute effect being reversible.
Mannitol had a direct osmolarity-independent cilio-stimulatory effect at lower % solutions and a reversible cilio-inhibitory effect at higher % solutions, and prolonged exposure to mannitol inhibited CBF reversibly. Both the acute and prolonged effects of mannitol compared to dextran and saline on CBF of HBEC in vitro, imply a unique mechanism of action for mannitol on ciliary beating and might contribute to the improved clearance observed in mannitol-treated patients.
吸入高渗盐水和甘露醇可改善支气管扩张症患者的黏液纤毛清除功能，但人们对这些化合物的相对渗透压强度如何影响纤毛上皮细胞（ciliated human bronchial epithelial cells，HBEC）的纤毛摆动频率（cilary beat frequency，CBF）知之甚少。本研究旨在比较渗透压相当的溶液对 HBEC 的 CBF 的体外直接作用。
急性（10、30 分钟）将 HBEC 暴露于等渗盐水（0.03-0.48%）、甘露醇（0.19-3%）和葡聚糖（10%-39.39%）的可比渗透压溶液中。还比较了高百分浓度溶液的效果、反应的可逆性和延长的处理（15-20 小时）。在基线和所有时间点使用数字视频显微镜测量 CBF。
HBEC 的 CBF 在急性暴露于甘露醇（0.19%、0.38%）后显著增加，在葡聚糖中降低，在盐水中不变。高渗透压浓度下（3%、6%），长时间暴露于甘露醇可可逆地抑制 CBF。相比之下，急性和长时间用 39.39%葡聚糖（相当于 3%甘露醇）处理可不可逆地降低 CBF。此外，1%盐水（相当于 6%甘露醇）的急性和长时间处理均可抑制 CBF，但仅急性作用是可逆的。
甘露醇在较低浓度时具有直接的渗透压非依赖性纤毛刺激作用，在较高浓度时具有可逆的纤毛抑制作用，并且长时间暴露于甘露醇可可逆地抑制 CBF。甘露醇对 HBEC 的 CBF 的体外急性和长期作用与葡聚糖和生理盐水相比，暗示了甘露醇对纤毛运动的独特作用机制，这可能有助于解释甘露醇治疗患者的清除功能改善。
