View Abstract

A3811 - Ciliary Activity of Bronchial Epithelium Under Experimental Cold Stress In Vitro
Author Block: J. M. Perelman1, A. N. Odireev2, K. F. Kilimichenko1, N. S. Bezrukov2, D. E. Naumov2, V. P. Kolosov2; 1Laboratory of Functional Research of Respiratory System, Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveschensk, Russian Federation, 2Laboratory of Prophylaxis of Nonspecific Lung Diseases, Far Eastern Scientific Center of Physiology and Pathology of Respiration, Blagoveschensk, Russian Federation.
RATIONALE. In patients with asthma, inhalation of cold air often leads to bronchoconstriction, thus increasing the frequency of seasonal exacerbations. It is known that prolonged effect of cold trigger on the mucosa of the respiratory tract is accompanied by morphofunctional and secretory disorders and the development of mucociliary insufficiency. However, the role of dysfunction of the bronchial ciliated epithelium (BCE) in the formation of mucociliary disorders during cold exposure has not been fully established. The aim of the study was to investigate the nature and severity of changes in the ciliary motility of the BCE under the influence of a cold stimulus in vitro. METHODS. Five volunteers with asthma underwent a bronchoscopy with biopsy of the lobar bronchus mucosa. The biopsy specimens were placed in a Hank’s balanced salt solution (HBSS) on a slide, located on the thermal stage, used to simulate the effect of various temperature on the BCE. Ciliary beat frequency (CBF, Hz) was recorded using a microscope, high-sensitivity digital camera and computer with specially developed software. The initial recording of CBF was performed at 24°C, after which the temperature of HBSS was gradually increased to physiological level and repeated recording was made at the control points (28°C and 36°C). Then, the temperature of the solution was lowered and CBF was registered again at 28°C, 21°C and 17°C. RESULTS. The initial CBF of the BCE varied from 2.70 to 5.04 Hz with average of 3.87±1.17 Hz (M±m). There was a statistically significant increase in CBF when the solution was heated: at 28°C it was 4.99±1.14 Hz (p=0.045) and remained at this level up to 36°C (5.00±1.06 Hz). A gradual decrease in the solution temperature produced a reduction in CBF in comparison with the physiological conditions: 28°C - 4.52±0.92 Hz (p=0.068), 21°C - 3.74±0.30 Hz (p=0.017) and 17°C - 2.58±0.80 Hz (p=0.015). Thus, by the end of the experiment, CBF of the BCE decreased almost 2-fold. A mathematical model that characterizes the behavior of BCE cilia under cold stress was developed. CONCLUSIONS. The results of the study demonstrate a marked decrease in the motor activity of the BCE cilia under cold stress, which underlines a significant contribution of the functional disturbance of BCE to the pathophysiological mechanisms of hypersecretory disorders induced by inhalation of cold air. It is possible that thermosensitive TRPM8 receptors, localized in epithelial cells, participate in this process, what requires further study.