Inherent Differences In Upper And Lower Airway Ciliary Function

Objective:Mucociliary clearance (MCC) is the first line of defence in the respiratory system against attack by pathogens and pollutants in the environment. As the power source of MCC, ciliary beating plays a crucial role in keeping MCC normal. Even though it has been years since researchers started their studies on the mechanisms of ciliary beating, there is still a long way to go before we well understand them. It has been found in clinical practices that Chronic sinusitis (CRS) patients demonstrate a compromise of MCC, but they rarely have abnormal physical signs in lower airway MCC. This suggests there are different ciliary beating functions between upper and lower airway. Therefore, we compared ciliary beating functions in upper and lower airway under various circumstances, in order to clarify the difference does exist, and to find new ways to study ciliary beating functions via comparison.Methods:The Puff system was built to mimic the physiological process of sneeze. We observed the effects of puffing on murine nasal ciliary beating frequency (CBF). Utilizing Apyrase, Suramin, EGTA, BAPTA-AM and H-89, we studied the effects of ATP, calcium (Ca2+) and protein kinase A (PKA) in this response. We also compared the different responses of nasal and tracheal CBF by stimulation of sneezing. Sisson-Ammons video analysis system was used to compare the basal CBF of upper and lower airway and intracellular Ca2+ of these cells were examined by fura-2 fluorescein. Murine septal and tracheal cultures were evaluated for basal and stimulated CBF before and after exposure to conditioned media from Pseudomonas. Additionally, the attachments of Pseudomonas to upper and lower airway cultures were assessed following pretreatment with conditioned media.Resutls:The ratio of CBF after puffing to the one before puffing in the nasal group was 1.78±0.05, n=10, and the blockers of ATP, Ca2+ and PKA could inhibit this stimulation. The same ratio in the tracheal group was only 1.21±0.03, n=10, p＜0.01. The CBF of tracheal epithelium was about twice as high as that of nasal epithelium in both mucosa and cultures. The intracellular Ca2+ concentration of tracheal epithelium was 91.06±9.85nM, n=4, and the one in nasal epithelium was 54.90±2.52 nM, n=4, p＜0.05. Lower airway cultures demonstrate resistance to Pseudomonas secreted cilio- toxins not evident in upper airway cultures. Furthermore, following challenge with viable pseudomonas, significantly more bacteria attach to the upper airway cultures compared to the lower airway cultures.Conclusion:There was inherent differences between upper and lower airway ciliary function. The stimulated CBF of nasal epithelium in response to "sneeze" was obviously higher than the tracheal epithelium in the same response. The basal CBF of tracheal ciliary cells was about twice as high as the one of nasal ciliary cells. Pseudomonas secreted cilio-toxins could decrease the basal CBF of nasal epithelium, and could inhibit the CBF stimulation after puffing, while tracheal epithelium demonstrated resistance to Pseudomonas secreted cilio-toxins.