Source: Annual Congress 2010 - Pathology of lung cancer
Disease area: Airway diseases

Abstract

The purpose of this investigation was to quantify the effects of cisplatin on mucociliary function. Further we measured the cisplatin-induced changes in the cytoplasmic calcium concentration which may be the cause of variations of ciliary beating and thus mucociliary function. Nasal epithelium from eight healthy donors was cultivated with its own mucus. Nasal epithelium spheroids (NES) were randomly assigned to incubation with cisplatin (2µg/ml for 3 hours; n=24) or controls (n=29). The rotation frequency and mucociliary transport velocity (MTV) of NES was measured at 37°C prior to and after adding 0.5 mmol/l ATP. In the 2^nd. part of our study the spheroids were randomized to incubation with (n=24) and without (n=22) cisplatin. They were loaded with the calcium indicator dye Fluo-4 AM (10µM) for 45 min at 37°C and washed with sHBSS for further 45 min. Fluorescence intensity of NES was measured using a CCD-camera.
Results: NES incubated with cisplatin had a lower rotation frequency than control-NES (2,61 ±0,26 vs. 3,15 ±0,28; mm/min.; mean ± SE). We used a linear mixed model to statistically analyze the changes of rotation frequency over time. We showed a significant decrease (pval 0,008) of MTV during the observation time in both groups. In control-NES we observed a significantly higher rotation frequency than in Cisplatin treated-NES after ATP. After incubation with cisplatin NES had significantly more calcium in the cytoplasm (F/Fo mean 6,34 ± 2,76) compared to control-NES (F/Fo mean 5,03 ±1,72) (pval 0,003, t-test).
Conclusions: Despite the increase of free calcium in the cytoplasm after incubation with cisplatin, mucociliary function worsens. The toxic effect of cisplatin on the cilia propably prevails.

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Citations should be made in the following way:
M. Petrova, A. Bergner, F. Tian, R. M. Huber, F. Gamarra (Munich, Germany). Acute effects of cisplatin on mucociliary function: In vitro measurements. Eur Respir J 2010; 36: Suppl. 54, 3257

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